Final Exam PHGY 170 Mod 4-6 Flashcards
(188 cards)
1
Q
Cytoskeleton
A
- Is a network of structural proteins that are found in all cell types
- functions such as signalling and vesicular transport
- defines shape of cell
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Q
Cytoskeleton structural proteins
A
Intermediate filaments
Microtubules
Actin
3
Q
Cytoskeleton: intermediate filaments
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Primary purpose of intermediate filament is to add mechanical strength to cells
4
Q
Cytoskeleton: microtubules
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Primary purpose of microtubules is to support trafficking within cells
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Cytoskeleton: actin
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Primary purpose of Aston is to support cellular motility or other large scale movements like contraction
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Q
Three types of cytoskeleton protein function
A
Binding
Conformation
Function
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Q
Cytoskeleton protein function: binding
A
Bind to a target like another protein to form polymers
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Q
Polymers
A
Molecules made of a large number of repeating units
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Cytoskeleton protein function: conformation
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When cytoskeleton proteins bind they undergo conformational changes
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Cytoskeletal protein function: function
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Function of these proteins is defined by the number and type of cytoskeletal proteins that are bound
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Major classes of intermediate filaments
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Classes: 1-6
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Intermediate filaments: class I
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Acidic keratins
Epithelial cells
Tissue strength and integrity
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Intermediate filaments: Class II
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Basic keratins
Epithelial cells
Tissue strength and integrity
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Q
Intermediate filaments: Class III
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- Desmin, GFAP, vimentin, periphevin
- muscle, glial cells, mesenchymal cells, perphevin neurons
- sarcomere organization, integrity
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Q
Intermediate filaments: class IV
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- neurofilaments
- neurons
- axon organization
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Intermediate filaments: class V
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- lamins
- nucleus
- nuclear structure and organization
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Intermediate filaments: class VI
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- nestin
- neurons
- axon growth
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Two most common intermediate filaments
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Class I and class II
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Secondary structure of intermediate filaments
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A-helices
B-sheets
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A-helices
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A helix is a tight coil that forms hydrogen bonds with the backbones of every fourth amino acid
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B-sheets
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Planes are formed between rows of amino acids with hydrogen bonds between the backbones
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Tertiary and quaternary structure of intermediate filaments
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Monomer
Dimer
Tetramer
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Monomer
A
The coiled monomer is the tertiary structural level
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Dimer
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Two coiled monomers form a dimer by wrapping around eachother
Allows for maximum contact between two peptides
A quaternary structure
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Tetramer
Two diners assemble in an antiparallel staggered manner.
Fundamental building block of intermediate filaments
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Intermediate filaments (tetramers) stage 1
The formation of what is called a unit length filament. Formed by eight tetramers coming together
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Intermediate filaments (tetramers) stage 2
Unit length filaments come together to form an immature filament. These interact loosely end to end
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Intermediate filaments (tetramers) stage 3
Immature filament compacts to form a mature filament.
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Three specialized intermediate filaments
Lamins
Desmins
Keratins
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Lamins
A type of intermediate filament found solely in the nucleus that forms the nuclear matrix a dense network to protect chromatin
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Desmins
A type of intermediate filament that does not form long thin filamentous structures but more so connects different cellular structures together. It is important for muscle structural integrity
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Keratin
An important intermediate filament that binds to desmosomes to form a complex. Keratin makes up hair skin and nails
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Intermediate filament assembly order
Monomers
Dimers
Tetramer
Unit length filament
Immature filament
Mature filament
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Microtubules
Cellular trafficking, vesicles, cellular organelles within the cytoplasm
Not random they define how things move throughout
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Microtubule organizing centre
Microtuble assembly here they require many proteins
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Tubulins
Composed of dimerized proteins
Very large family of cellular proteins
Two specific tubulins: a-tubulin and B-tubulin
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Steps of microtubule polymerization
Dimers form polymers
Polymer growth
Protofilament tubes
Assembly/disassembly
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Dimers form polymers
Dimers will spontaneously assemble into unstable polymers that can quickly fall apart
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Polymer growth
Once a polymer of at least six dimer subunits forms it is more stable and it may grow laterally and longitudinally. This forms protofilament
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Protofilament tubes
Will form a sheet and will assemble into a tube of 13 Protofilament. This is the nucleation site for microtubles elongation.
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Assembly/disassembly
At the ends of microtuble dimers continue to come and go. If the rate of assembly is greater than disassembly the microtubules grows if slow rate it disassemblies
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Microtubles assembly
When GTP is bound to b-tubulin dimer polymerization is favoured and the diners will attach to eachother
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Microtubule disassembly
When b-tubulin GTP is hydrolysed to GDP, the dimer undergoes a conformational change that promotes depolumerization
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Microtuble polarity
Microtuble formed by end to end polymerization of dimers, ends are polarity. One end is plus the other minus. Growth occurs at both ends but at different rates extending faster from the plus end
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Microtubule dynamic instability
Microtubule are very responsive and have the ability to grow and shrink or change directions to respond to changes in cellular environment
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Microtubule catastrophe
GTP is converted to GDP on the tubulin dimers fall off resulting in rapid depolyerization to tubulin dimers at the plus end resulting in shortening of Microtuble
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Measures against microtubule catastrophe
Capping
Rescue
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Catastrophe aversion capping
Once a microtuble is of desired length the plus end can be bound by capping proteins. Which add tremendous stability and will keep them polymerized
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Catastrophe reversal rescue
Occur spontaneously if there are enough GTP bound dimers present thus halting catastrophe
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Motor proteins
Control trafficking by binding to cargo then bind to microtubule and walk along them
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Two common types of microtubule motor proteins
Kinesin
Dynein
Kinesin walks towards plus end of microtubule well dynein moves to the minus end
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Structure of dynein
Microtubule binding domains
Stalk
Head
Stem
Tail
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Structure of Kinesin
Microtubule binding domains
Head
Stalk (coiled)
Tail
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Walking motor proteins step 1
Head 1 is bound to the microtubule and head 2 is bound to ADP
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Walking motor proteins step 2
The walking movement is initiated by ATP binding to head 1 which causes a conformational change that includes head 2 swinging around
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Walking motor proteins step 3
Once head 2 is over binding site it binds to the microtubule and releases the ADP
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Walking motor proteins step 4
The ATP at head 1 then undergoes hydrolysis so it is now ADP bound to head 1 which causes it to release from the microtubule
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Walking motor proteins step 5
The entire process is then repeated but with ATP now binding to head 2 causing head 1 to swing around
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Composition of actin and microtubules
Both are composed of globular proteins
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Movement of actin and microtubules
Motor proteins are used to initiate movement along both cytoskeletal proteins
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Actin monomers
Basic building block
Long thin filaments
Have high tensile strength
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Tensile strength
Resistance to breaking under tension
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Actin polymerization
The binding of ATP promotes assembly aka polymerization. Where the binding of ADP discourages polymerization which may lead to disassembly
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Three stages of actin polymerization
Stage 1: nucleation
Stage 2: elongation
Stage 3: steady state
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Actin polymerization: stage 1 nucleation
Two actin monomers can dimerize but nucleation occurs when a third actin monomer binds to the dimer forming a nucleus trimer
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Actin polymerization: stage 2 elongation
Additional actin monomers added to nucleus. Actin elongates occurring in both directions
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Actin polymerization: stage 3 steady state
Eventually the rate of assembly equals the rate of disassembly and net actin elongation ceases
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Actin treadmilling
Same rate of removal and addition to the ends of actin
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Actin binding proteins
Monomer binding proteins
Nucleating proteins
Capping proteins
Severing and depolymerization proteins
Cross linking proteins
Membrane proteins
Actin binding motor proteins
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Actin binding proteins
Monomer binding proteins
Nucleating proteins
Capping proteins
Severing and depolymerization proteins
Cross linking proteins
Membrane proteins
Actin binding motor proteins
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Actin binding proteins: monomer binding
Proteins that bind directly to the actin monomers and influence polymerization
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Actin binding proteins: nucleating protein
Proteins that bind to actin polymers to increase their stability and can allow for growth of a new branch
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Actin binding proteins: capping proteins
Proteins the bind to the plus or minus end and can stabilize the polymers to prevent disassembly and further assembly
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Actin binding proteins: severing and deploymerizatiin proteins
Proteins that can bind to the actin polymer and sever or induce disassembly respectively
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Actin binding proteins: cross linking proteins
Proteins that allow the side to side linkage of actin polymers to form bundles of actin filaments
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Actin binding proteins: membrane anchors
These link actin filament to nonactin structural proteins
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Actin binding proteins:actin binding motor proteins
Proteins that bind to the actin filament and allow movement.
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Myosin
Most studied actin binding protein
18 different families of myosin broken into subunits called light chain or heavy chain
Have three different domains motor, regulatory, tail domains
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Myosin: motor domain
Formed by heavy chain binds to the actin filament and ATP
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Myosin: regulatory domain
Formed by a heavy chain and two light chains moves back and forth as the myosin moves along an actin filament
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Myosin: tail domain
Binds to other cellular proteins or other myosin
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Hydrolysis movement of actin binding protein
With ATP bound to the motor domain, the myosin is unbound to the actin filament. Hydrolysis of ATP to ADP and inorganic phosphate cause a conformational shift in the regulatory domain swing like a lever
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Actin binds movement of actin binding. Motor protein
- Motor domain then binds to the actin filament.
- The inorganic phosphate is released from myosin causing another conformation all change and pulling the myosin along the actin filament
- ADP is then released and the binding of new ATP causes myosin to unbind from actin
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Movement of myosin
Moves toward the plus end of actin
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Three types of actin filaments responsible for cellular migration
Filopodia
Lamellipodia
Stress fibres
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Filopodia
Are thin parallel bundles of filaments. All have same polarity with plus end facing membrane. They extend in the direction of the intended movement
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Lamellipodia
Are large sheet like bundles of actin filaments. Are polar with plus end towards plasma membrane. Form broader structures
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Stress fibres
Forms around integrins. Plus end towards the cytosol. Rich in motor proteins and anchored to the integrins
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Two overarching phases of the cell cycle
Interphase
Mitosis
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Interphase cell cycle
Made up three phase G1, S and G2.
Most of cells life in G1
They are actively living or preparing to divide
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Mitosis cell cycle
Cells dividing
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Cell cycle phase
G1 phase
G0 phase
G1/S checkpoint
S phase
S/G2 checkpoint
G2 phase
G2/M checkpoint
M phase
Mitotic spindle checkpoint
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Cell cycle G1 phase
Cells are not actively dividing
G1 cells are active and growing but pass through check point to start cell division
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Cell cycle G0 phase
Resting state found in nerve and muscle cells
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Cell cycle G1/S checkpoint
Cell proteins check for DNA damage before the cell can move to S phase
Known as start point, activates a range of signals to allow cells to divide
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Cell cycle S phase
Synthesis, the cell replicates its entire genome for division
The centrosome is duplicated
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Cell cycle S/G2 checkpoint
DNA integrity is checked before the cell moves to G2
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Cell cycle G2 phase
Last chance for cells to grow before division cytoplasm and endomembrane system increased
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Cell cycle G2/M checkpoint
Triggers large scale rearrangement to the structure of the cell which facilitates mitosis. Increase in cell volume
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Cell cycle M phase
Mitosis occurs
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Cell cycle mitotic spindle checkpoint
Ensures all chromosomes are properly separated
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P53 protein
Is a tumour suppressor protein that ensures cells with damaged DNA done divide
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P53 protein
Is a tumour suppressor protein that ensures cells with damaged DNA dont divide
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LFS
Genetic condition that gives individuals a greater risk of developing cancer.
Often have a mutation in the gene that codes p53
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Mitosis
When a parent cell divides into two daughter cells
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Mitosis phases
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
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Mitosis: interphase
G1, S, G2 all occur in interphase
At this time cells are not dividing they are growing and preparing to divide
DNA replication occurs
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Mitosis: prophase (chromosome condensation)
- chromosomes densely packed into chromatids
- each chromosome has been replicated (sister chromatids)
- connected structural point called centromere
- transcription is shut down, endo system dissolves and mitochondria distribute to give each daughter cells the organelles to live
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Mitosis: prophase (after condensation)
- nuclear envelope dissolves, releasing chromosomes into cytosol
- centrosomes are moved to opposite ends of the cell by tubulin and motor proteins
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Chromatid
One of two identical copies of DNA making a duplicated chromosome which are joined at their centromeres for cell division
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Centromere
Region in the chromosome that holds sister chromatids together
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Kinetichore
Typically located near the centromere it is the location of attachment of spindles during cell division
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Mitosis: prometaphase
- each pair will have two kinetochore which binds to chromatids of centromere
- kinetochores use ATP to polymerize and depolarize microtubule spindle fibres allowing chromosomes to move within cell
- eventually moving to centre of cell for next stage metaphase
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Mitosis: Metaphase
- chromosomes have arrived at spindle equator
- chromosomes have attached to kinetochore microtubules pulling equally in both directions
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Mitosis: Anaphase
- proteins that bind sister chromatids are cleaved dividing each chromosome into two
- reaching final step for cell division and reformation of nucleus
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Mitosis: telophase
- reorganization of cell, nuclear membrane is reformed around chromosomes
- cytoskeleton reform
- endo system reform
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Mitosis: cytokinesis
- contractile ring forms where spindle equator was located
- ring tightens cell is divided roughly in half
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Extracellular communication
Is communication that occurs when a signal is received from outside the cell itself
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Intracellular communication
To collect info from multiple sources, synthesize this information then make decision on how to respond to the info
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Four types of extracellular communication
Autocrine
Paracrine
Endocrine
Neurotransmitters
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Autocrine
Substances are released by a cell and have an effect on the same cell
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Paracrine
Substances are released by a cell and have an effect in nearby cells
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Endocrine
Substances are released by a cell and have effect in distant cells
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Neurotransmitter
Substances are released by a nerve terminal into the synapse
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Nerve terminal
The end of a nerve cell
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Components of signalling pathway: intracellular
The signal
The receptors
Signalling protein
Second messengers
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Intracellular signalling pathway: the signal
Can be either membrane permeable or membrane impermeable
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Intracellular signalling pathway: the receptors
Interact with the signal
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Intracellular signalling pathway: signalling proteins
Are proteins that help conduct the signal intracellularly
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Intracellular signalling pathway: second messengers
Are non protein that help conduct the signal intracellularly
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Structure of a signalling pathway
Membrane permeable signal molecule
Membrane impermeable signal molecule
Signalling proteins and second messengers
Cytoplasmic effects
Nuclear effectors
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Membrane permeable signal molecule
Molecules bind to receptor protein in the cytosol
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Membrane impermeable signal molecule
Bind to transmembrane cell surface receptor proteins which then activate second messengers
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Signalling proteins and second messengers
Amplify process and distribute incoming signals from both classes of signal receptor proteins
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Cytoplasmic effectors
Some signals are sent to effector proteins in the cytosol typically a fast short lived response to the activation of signalling pathway
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Nuclear effectors
Some signalling pathways terminate at effectors in the nucleus. These effectors are transcription factors that control gene expression. Results in slower more prolonged response
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Signal transduction
Is a signal activating a receptor that can be linear, convergent, divergent or multi branched
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Linear
One receptor interacts with one signalling protein or second messenger
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Convergent
Several receptors will share common signalling proteins or second messengers
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Divergent
A single receptor can interact with multiple signalling proteins or second messengers
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Multi branched
A combination of convergence and divergence may be happening all at the same time
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Stages of signal transduction
Signal (ligands)
Receptors
Signalling proteins
Second messengers
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Signal (ligands)
Arise from extracellular space must bind to sensor
A substance that forms complex bio molecules
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Three types of signals
Membrane impermeable
Membrane permeable
Physical signals
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Signal: membrane impermeable
Majority of molecules/ligands are impermeable
Are molecules that cannot penetrate membrane bind to receptor proteins on cell surface
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Signal: membrane permeable
Signal molecules/ligands are mainly steroids
Able to penetrate membrane
Not limited to membrane receptors and interact with cytosolic receptors
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Signal: physical
Pressure
Temp
Light
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Receptors
Often found on the plasma membrane but can be found in cytoplasm of cell
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Types of receptors
G-protein coupled receptors
Ion channels
Guanylate Cyclase
Protein kinase receptors
Transmembrane scaffolds
Nuclear receptors
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G protein coupled receptors
- Role in cellular transduction
- Located on cell surface
- Respond to hormones, neurotransmitters
- immune responses and metabolism
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Ion channels
- select specific ions
- key role in nerve impulse and muscle contraction
- sodium and potassium channels
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Guanylate cyclase
- conversion of GTP
- vasodilation, neuronal signaling, cardiac function
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Protein kinase receptors
- Cellular surfeit receptors that assist with external signals that activate intracellular pathways
- 2 types tyrosine and threonine/serine kinase
- help with cell growth and metabolism
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Transmembrane scaffolds
- proteins throughout the cell membrane that form clusters of receptors
- role in organization of signaling pathways
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Nuclear receptors
Located In the cytosil of cells bind to DNa to help gene expression
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Mobility
- Signalling proteins are highly mobile
- diffuse rapidly through the cytosol and move rapidly within plasma membrane
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Catalysis
Signalling proteins are either enzymes that can catalyze chemical reactions for signal amplification or they are capable of binding to enzymes
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Two types of signalling proteins
Monomeric G-proteins
Heterotrumeric G proteins
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Monomeric G proteins
Are single polypeptides that contain at least two different binding sites in GTP or GDP
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Heterotrumeric G proteins
Contain three polypeptides similar function to Monomeric G proteins
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Four step to activate G proteins
Binding
Separation
Propagate
Cleave and reform
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G protein activation: binding
- Heterotrimer containing alpha and beta subunits is bound to GDP
- when ligand binds the receptor changes to interact with hetero G protein
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G protein activation: separation
- the receptor protein causes exchange of GDP with GTP on alpha subunit
- hetero separates alpha and beta
- G proteins active
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G protein activation: propagate
- while separated the alpha and beta bind downstream to targets
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G protein activation: cleave and reform
- alpha subunit cleaves GTP to form GDP
- alpha and beta bind to reform heterotrimer
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Five signalling proteins
Calcium binding
Adenylyl cyclase
Protein kinases
Lipid kinases
Adaptor proteins
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Signalling protein: calcium binding
Ion on cell kept in low intracellular concentrations
- results in downstream signalling
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Signalling protein: adenylyl cyclase
Binds to alpha subunit of hetero G protein
Converting ATP to cAMP
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Signalling protein: protein kinases
Enzymes that phosphorylation proteins resulting in activation of downstream signalling
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Signalling protein: lipid kinases
Phosphorylation phospholipids in the cytoplasmic leaflets of the membrane
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Signalling protein: adaptor proteins
Allow cascades to be associated in the right space and turn to fulfill their task when and where they are needed
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Second messengers
Non protein ions and molecules which relay signalling info from signalling proteins to cellular targets
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Heterotrimeric G protein signalling cascade
GPCRS
cAMP
PKA
CREB
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Heterotrimeric G protein signalling cascade: GPCRS
- Is initiated by the binding of ligand to GPCR
- receptor allows receptor protein to interact with Hetero G protein
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Heterotrimeric G protein signalling cascade: CAMP
- ligand bound receptor stimulates the replacement of GDP for GTP
- G protein dissociate from receptor and leave beta and alpha subunit
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Heterotrimeric G protein signalling cascade: PKA
ligand bind yet to another signalling pathway
- causes protein to dissociate and release the active catalytic subunit
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Heterotrimeric G protein signalling cascade: CREB
- once PKA, CREB binds with CBP the two proteins can interact with DNA to initiate transcription
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Three types of cells to handle dangerous cargo
Lysosomes
Proteasomes
Perixisomes
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Lysosomes
Are organelles that break down misfolded and damaged organelles nucleic acids and lipids
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Proteasomes
Are protein complexes that specifically break down damaged and misfolded proteins in the nucleus and cytosol
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Peroxisomes
Small membrane enclosed organelles that handle dangerous free radicals
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Two forms of cell death
Apoptosis
Necrosis
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Apoptosis
Programmed cell death used to protect the body from damaged cells that no longer function properly
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Necrosis
Accidental cell death
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Mechanism of necrosis’s
Damage
Swelling
Destruction
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Mechanism of necrosis: damaged
Cells are damaged beyond repair from toxins, radiation, freezing, trauma
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Mechanism of necrosis: swelling
Organelles begin to lose their structures and swell DNA is degraded
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Mechanism of necrosis: destruction
Cell membrane and remaining organelles lose structural integrity, contents spill out of cell causing inflammation. Near by cells exposed causing apoptosis of those cells
