Cytoskeleton I and II (Cell Bio) Flashcards

1
Q

CYTOSKELETON

The cytoskeleton determines cellular * ? * and * ? *

A detailed network of protein filaments (intermediate, microtubules, actin) that extends throughout the ?.

All three cytoskeleton filament systems must normally function collectively to give a cell its ?, ?, and ability to ?

Importance
 Cells need proper ? in space
 Need to interact with ?
 Need to interact with their ?

apical is the top or bottom part?

A

CYTOSKELETON

The cytoskeleton determines cellular * ORGANIZATION * and * POLARITY *

A detailed network of protein filaments (intermediate, microtubules, actin) that extends throughout the cytoplasm.

All three cytoskeleton filament systems must normally function collectively to give a cell its strength, shape, and ability to move

Importance
 Cells need proper organization in space
 Need to interact with each other
 Need to interact with their environment

apical is the top PART as seen in pic and basal lamina the bottom part

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2
Q

CYTOSKELETON
Facilitates the existence of special structures:

  • ? - cellular membrane protrusion, increase surface area
  • ? - special adhesive protein complexes that help maintain mechanical integrity
  • ? Junctions - protein complexes that occur at cell-cell junctions
  • ? and ? Membranes - Apical (towards the lumen) Basolateral (away from lumen)

The ? that make up the ? of the ? can form polarized and self- organized structures that can be ?, allowing the cell to rapidly modify its ? and ? under different conditions.

A

CYTOSKELETON
Facilitates the existence of special structures:

  • microvilli - cellular membrane protrusion, increase surface area

(prebiotics help increase the microvilli SA)

  • desmosomes - special adhesive protein complexes that help maintain mechanical integrity
  • adherens Junctions - protein complexes that occur at cell-cell junctions
  • apical and basal Membranes - Apical (towards the lumen) Basolateral (away from lumen)

The proteins that make up the filaments of the cytoskeleton can form polarized and self-organized structures that can be highly dynamic, allowing the cell to rapidly modify its structure and function under different conditions.

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3
Q

CYTOSKELETON
THE CYTOSKELETON ENABLES A CELL:

  • To organize and maintain its correct ? and ? (external/internal)
  • To resist ? deformation
  • To stabilize ? and its ? (by associating the cell to other ? and to its surrounding extracellular tissues)
  • To change its shape for ? and ?

THREE DIFFERENT TYPES OF FILAMENTS COMPOSE THE CYTOSKELETON:
which are?

A

CYTOSKELETON
THE CYTOSKELETON ENABLES A CELL:

  • To organize and maintain its correct shape and structure (external/internal)
  • To resist mechanical deformation
  • To stabilize itself and its environment (by associating the cell to other cells and to its surrounding extracellular tissues)
  • To change its shape for movement and migration

THREE DIFFERENT TYPES OF FILAMENTS COMPOSE THE CYTOSKELETON:
which are: actin filaments, intermediate filaments, microtubules
(AF and IF responsible for mechanical resistance of cell)

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4
Q

CLASSIFICATION OF CYTOSKELETON COMPONENTS

IMMUNOFLUORESCENCE STAINING DETECTION OF * IMP ? FILAMENTS (MICROFILAMENTS) & *
- immunoflu.. attached to actin filaments

A
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5
Q

** Actin filaments determine the ? of a cell and are necessary for cell ? **

Microtubules determine the ? of membrane-enclosed organelles, direct ? transport, and form the ? spindle

Intermediate filaments provide ? strength

A

** Actin filaments determine the shape of a cell and are necessary for cell locomotion **

Microtubules determine the position of membrane-enclosed organelles, direct intracellular transport, and form the mitotic spindle

Intermediate filaments provide mechanical strength

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6
Q

CYTOSKELETON

 Actin filaments and microtubules are built from subunits that are ? and ?.

 Intermediate filaments are made up of smaller subunits that are ? and ?

All three filaments form ? assemblies of subunits that ?-associate, using a combination of ? and ? protein contacts.

A

CYTOSKELETON

 Actin filaments and microtubules are built from subunits that are compact and globular

 Intermediate filaments are made up of smaller subunits that are elongated and fibrous

All three filaments form helical assemblies of subunits that self-associate, using a combination of end-to-end and side-to-side protein contacts.

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7
Q

** MICROFILAMENTS - ACTIN STRUCTURE & FUNCTION **

Found in eukaryote cells, actin performs a ? range of ? in cells

Essential for:
 ? support
 ? → cell crawling, engulfing, migrate, muscle movement
 Cell ?, ? → microvilli

ACTIN- STRUCTURE & FUNCTION
Form a tough, but flexible framework
-> G-Actin subunits are ? and ?. Form a tight, right-handed helix called filamentous actin (F-actin)
* Actin-Filament (F-Actin) consists of 2 parallel ?
* rigid or flexible? structure
* Usually shorter than ?

A

** MICROFILAMENTS - ACTIN STRUCTURE & FUNCTION **

Found in eukaryote cells, actin performs a wide range of functions in cells

Essential for:
 mechanical support
 movements: cell crawling, engulfing, migrate, muscle movement
 Cell shape and structure → microvilli

ACTIN- STRUCTURE & FUNCTION
Form a tough, but flexible framework
-> G-Actin subunits (basic parts) are compact and globular. Form a tight, right-handed helix called filamentous actin (F-actin)
* Actin-Filament (F-Actin) consists of 2 parallel protofilaments
* flexible structure
* Usually shorter than microtubules

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8
Q

ACTIN- POLYMERIZATION

Actin filaments can grow by adding more actin monomers at either end (-) or (+):

o Nucleation
o Elongation
o Steady State

Each free actin monomer carries a tightly bound ?

o ATP bound actin has a higher affinity for the ? subunits and remains ? in the filament

o ADP bound actin can ? from the filament

 Hydrolysis of ATP->ADP
- Reduces strength of binding b/t monomers
- Decreases polymer ?

Accessory proteins regulate actin ?

 ? – inhibits nucleation
 ? – accelerate depolymerization

A

ACTIN- POLYMERIZATION

Actin filaments can grow by adding more actin monomers at either end (-) or (+):

o Nucleation
o Elongation
o Steady State

Each free actin monomer carries a tightly bound ATP

o ATP bound actin has a higher affinity for the neighbouring subunits and remains stable in the filament

o ADP bound actin can dissociate easily from the filament

 Hydrolysis of ATP->ADP
- Reduces strength of binding b/t monomers
- Decreases polymer stability

Accessory proteins regulate actin dynamics

 profilin – inhibits nucleation
 cofilin – accelerates depolymerization

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9
Q

ACTIN – Polymerization and depolymerization

Actin filaments can polymerize to ? or ?

ATP bound actin has a higher affinity for the ? subunit and remains ? in the filament

? bound actin can more easily dissociate from the filament

ACTIN – STRUCTURE (Cell shape):
?-forming crosslinker: (more ?)
?-forming crosslinker: (?)

Actin filaments exist in different ? in cell

Formation depends on actin ? (actin- binding proteins)

examples of cross-linking proteins
o Fascin: ? bundles
o Filamin: 3D ?-forming networks (At 90 degree angle)

A

ACTIN – Polymerization and depolymerization

Actin filaments can polymerize to grow or depolymerize (break down into polymers)

ATP bound actin has a higher affinity for the neighbouring subunit and remains stable in the filament

ADP bound actin can more easily dissociate from the filament

ACTIN – STRUCTURE (Cell shape):
bundle-forming crosslinker: (more rigid)
gel-forming crosslinker: (networks)

Actin filaments exist in different spatial arrays in cell

Formation depends on actin crosslinking proteins (actin-binding proteins)

examples of cross-linking proteins
o Fascin: linear bundles
o Filamin: 3D gel-forming networks (At 90-degree angle)

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10
Q

ACTIN – Microvilli support

  • Actin filaments are cross-linked by
    o ? packed ? arrays
  • Proteins involved in crosslink:
    o are big or small? flexible or rigid?
    o Force filaments to align closely Example: ?, fimbrin
  • Can support the way ? project
  • Can also ? (associated with myosin I and calmodulin)

Gel-forming crosslinker

? crosslinked in a 3D-like meshwork with ? gel-like properties

Proteins involved in the network:
o small or large? and rigid or flexible?
o Crosslink more parallel or perpendicular?
o I.e., ?

A

ACTIN – Microvilli support

  • Actin filaments are cross-linked by
    o closely packed parallel arrays
  • Proteins involved in crosslink:
    o are small and rigid
    o Force filaments to align closely Example: villin, fimbrin
  • Can support the way microvilli project
  • Can also contract (associated with myosin I and calmodulin)

Gel-forming crosslinker

loosely crosslinked in a 3D-like meshwork with semisolid gel-like properties

Proteins involved in the network:
o large and flexible
o Crosslink more perpendicular
o I.e., Filamin

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11
Q

ACTIN – Cell movement

Actin crosslink and cell movement:

stress fiber: ? bundle
cell cortex: ? network
filopodium: ? bundle

A

stress fiber: contractile bundle
cell cortex: gel-like network
filopodium: tight parallel bundle

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12
Q

ACTIN – Cell movement

Three main processes are known to be essential for movement and all involve ACTIN

  1. The cell pushes out its protrusion at its ”?” or “? edge”
  2. These protrusions stick to the ? over which the cell crawls
  3. The rest of the cell drags itself ? by traction
  • IMP Examples of cells that do this:
    1. Carnivorous ?
    2. ? (WBC)
    3. ? axons in response to
    growth factors
    4. ?
A

ACTIN – Cell movement

Three main processes are known to be essential for movement and all involve ACTIN

  1. The cell pushes out its protrusion at its ”front” or “leading edge”
  2. These protrusions stick to the surface over which the cell crawls
  3. The rest of the cell drags itself forward by traction
  • IMP Examples of cells that do this:
    1. Carnivorous amoeba
    2. neutrophils (WBC)
    3. developing axons in response to
    growth factors
    4. fibroblasts
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13
Q

ACTIN - CELL DIVISION
CYTOKINESIS:

The part of cell division when the ? cell divides into 2 daughter cells

Following the completion of ? (nuclear division), a ? ring consisting of actin filaments and myosin (II) divides the cell in two:
* Cell membrane will grow inward (cleavage) and ? off

ACTIN - ASSOCIATED PROTEINS → MOTOR PROTEINS

Myosin, Kinesin & Dynein
* ? proteins that cause motion inside ? in association with parts of the ?
* All are ?
* ATP → ? energy (transport, muscle movement, beating of cilia and flagella)

** Actin associates with myosin to form ? structures
All ?-dependent motor proteins belong to the myosin family **

A

ACTIN - CELL DIVISION
CYTOKINESIS:

The part of cell division when the eukaryotic cell divides into 2 daughter cells

Following the completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin (II) divides the cell in two:
* Cell membrane will grow inward (cleavage) and pinches off

ACTIN - ASSOCIATED PROTEINS → MOTOR PROTEINS

Myosin, Kinesin & Dynein
* Motor proteins that cause motion inside cells in association with parts of the cytoskeleton
* All are ?
* ATP → ? energy (transport, muscle movement, beating of cilia and flagella)

** Actin associates with myosin to form contractile structures
All antin-dependent motor proteins belong to the myosin family (and not to the kinesin and dynein) **

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14
Q

ACTIN – Motor proteins: Myosin family

Myosin I
o #? head and a ?
o ? vesicles (tail can bind to)

Myosin II - MOST COMMON
o #? globular (ATPase) heads and ? tail
o Produces muscle contraction in some or most animal cells?
o In non-muscle cells: contractile ?-stress fibers

Myosin V
o ? transporter (i.e. RNA, Vesicles, Organelles, Mitochondria)
o ? keeping vesicles and organelles in the
?-rich ? of cells

A

ACTIN – Motor proteins: Myosin family

Myosin I
o 1 head and a tail
o transporting vesicles (tail can bind to)

Myosin II - MOST COMMON
o two globular (ATPase) heads and coiled tail
o Produces muscle contraction in most animal cells
o In non-muscle cells: contractile bundle-stress fibers

Myosin V
o Cargo transporter (i.e. RNA, Vesicles, Organelles, Mitochondria)
o Tether like keeping vesicles and organelles in the actin-rich periphery (outer limits of an area) of cells

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15
Q

ACTIN & MYOSIN IN MUSCLE

?: contractile elements of the muscle cell

  • Consists of a chain of tiny identical contractile units called ?
  • Sarcomeres- highly organized assembly of 2 types: ? and ?

Actin and Myosin - Muscle contraction

Sarcomeres:
Highly organized assembly of 2 types: actin and myosin II filaments
→it’s a ? unit

Contraction is caused by a * ? * shortening of all the sarcomeres
Caused by * ? * sliding past the myosin filaments

A

ACTIN & MYOSIN IN MUSCLE

myofibril: contractile elements of the muscle cell

  • Consists of a chain of tiny identical contractile units called sarcomeres
  • Sarcomeres- highly organized assembly of 2 types: actin and myosin II filaments

Actin and Myosin - Muscle contraction

Sarcomeres:
Highly organized assembly of 2 types: actin and myosin II filaments
→it’s a functional unit

Contraction is caused by a * simultaneous * shortening of all the sarcomeres
Caused by * actin filaments * sliding past the myosin filaments

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16
Q

Muscle contraction

Sliding Filament Model:
A process used by muscles to ?

 Myosin ? interact with the actin filaments
 The thin (actin) filament slides over the thick filament to cause ?
 Depends on sequence of molecular events: ?

Muscle stimulated → ? → ? walks along the ?
This happens over and over again (repeated cycles of attachment and detachment)
THUS, Sarcomere contracts

A

Muscle contraction

Sliding Filament Model:
A process used by muscles to contract

 Myosin heads interact with the actin filaments
 The thin (actin) filament slides over the thick filament (myosin) to cause tension
 Depends on sequence of molecular events: cross-bridge cycling

Muscle stimulated → contraction → myosin heads walk along the actin filament

This happens over and over again (repeated cycles of attachment and detachment)
THUS, Sarcomere contracts

17
Q

ACTIN - muscle contraction

  1. The myosin head has ATPase on it so when ATP binds to myosin head it hydrolyzyes into ADP and Pi
  2. The phosphorylated myosin head now attaches to thin (actin) filament and a power stroke occurs and ADP and Pi are released
  3. new ? then attaches to myosin and myosin head detaches
  4. ? of myosin head occurs
A

ACTIN - muscle contraction

  1. The myosin head has ATPase on it so when ATP binds to myosin head it hydrolyzyes into ADP and Pi
  2. The phosphorylated myosin head now attaches to thin (actin) filament and a power stroke occurs and ADP and Pi are released
  3. new ATP then attaches to myosin and myosin head detaches
  4. cocking of myosin head occurs
18
Q

ASSOCIATION OF TROPOMYOSIN AND TROPONINS WITH ACTIN FILAMENTS – Striated muscle

Tropomyosin binds lengthwise along * ? * filaments and is associated with a complex of three troponins:
* troponin I (TnI) - inhibitory
* troponin C (TnC) - calcium
* troponin T (TnT) - tropomyosin

In the absence of ?, the tropomyosin-troponin complex ? the binding of myosin to actin

Binding of ? to which Tn? moves the complex, freeing the myosin-acting binding site, and allowing ? to proceed

ACTIN AND MYOSIN- MUSCLE CONTRACTION

Signal from the ? system -> Triggers an ?

Then the following steps occur:
1. Electrical impulse → depolarize each
? → sarcoplasmic reticulum (main function is to store ? Ions)

  1. Release ?
  2. Ca+ + interacts with → ? complex- ?
A

ASSOCIATION OF TROPOMYOSIN AND TROPONINS WITH ACTIN FILAMENTS – Striated muscle

Tropomyosin binds lengthwise along * actin * filaments and is associated with a complex of three troponins:
* troponin I (TnI) - inhibitory
* troponin C (TnC) - calcium
* troponin T (TnT) - tropomyosin

In the absence of Ca+, the tropomyosin-troponin complex blocks the binding of myosin to actin

Binding of calcium to which TnC moves the complex, freeing the myosin-acting binding site, and allowing contraction to proceed

ACTIN AND MYOSIN- MUSCLE CONTRACTION

Signal from the nervous system -> Triggers an AP

Then the following steps occur:
1. Electrical impulse → depolarize each
myofibril → sarcoplasmic reticulum (main function is to store calcium Ions)

  1. Release calcium ions
  2. Ca+ + interacts with → troponin complex- tropomyosin
19
Q

Drugs that affect actin filaments and microtubules:

ACTIN-SPECIFIC DRUGS (know that these drugs will affect the cytoskeleton)

Phalloidin: binds and ? filaments

the ones below will have a strong impact on actin filament (shape and func. will be compromised)
Cytochalasin: caps filament plus ends
Swinholide: severs filament
Latrunculin: binds subunits and prevents their polymerization

Chemical compounds that stabilize or destabilize actin filaments are important tools in studies of the filaments’ dynamic ? and ? in cells.

PHALLOIDIN (from mushroom)
It can be used for staining ? filaments
-> Binds to all ? of actin filaments in many
different species of animals and plants (very specific)
-> Binds actin filaments and blocks ?

ALPHA-AMANITIN (not related to cytoskeleton)

The main toxic component of the death cap mushroom
-> inhibits RNA-polymerase II

A

Drugs that affect actin filaments and microtubules:

ACTIN-SPECIFIC DRUGS (know that these drugs will affect the cytoskeleton)

Phalloidin: binds and stabilizes filaments

the ones below will have a strong impact on actin filament (shape and func. will be compromised)
Cytochalasin: caps filament plus ends
Swinholide: severs filament
Latrunculin: binds subunits and prevents their polymerization

Chemical compounds that stabilize or destabilize actin filaments are important tools in studies of the filaments’ dynamic behavior and function in cells.

PHALLOIDIN (from mushroom)
It can be used for staining actin filaments
-> Binds to all variants of actin filaments in many
different species of animals and plants (very specific)
-> Binds actin filaments and blocks depolymerization

ALPHA-AMANITIN (not related to cytoskeleton)

The main toxic component of the death cap mushroom
-> inhibits RNA-polymerase II

20
Q

MICROTUBULES

Microtubules are polymers of the protein ?

The tubulin subunit is itself a ? formed from two closely related globular proteins called ?- tubulin and ? (each 445-450 amino acids length)

  • Each tubulin has a binding site for one ? molecule:

 ** IMP the GTP that is bound to ?-tubulin is trapped and is never ? neither ?; **
 the GTP in beta-tubulin may be in either the ? or the ? form and is ?

A

MICROTUBULES

Microtubules are polymers of the protein tubulin

The tubulin subunit is itself a heterodimer formed from two closely related globular proteins called alpha-tubulin and beta-tubulin (each 445-450 amino acids length)

  • Each tubulin has a binding site for one GTP molecule:

 ** IMP the GTP that is bound to alpha-tubulin is trapped and is never hydrolyzed nor exchanged **
 the GTP in beta-tubulin may be in either the GTP or the GDP form and is exchangeable

21
Q

Microtubules are hollow cylindrical structures built from ?.

Each composed of alpha- beta ? heterodimers (as it has both alpha and beta; its subunit is a microtubule) stacked head to tail and then folded into a ?

MICROTUBULES
How can microtubules grow and shrink?
 By a process called ?

Dynamic instability refers to the ? and ? at the ends of a ?.

 The microtubule can dynamically switch between ? and ? phases

A

Microtubules are hollow cylindrical structures built from protofilaments.

Each composed of alpha- beta tubulin heterodimers stacked head to tail and then folded into a tube

MICROTUBULES
How can microtubules grow and shrink?
 By a process called “dynamic instability”

Dynamic instability refers to the coexistence of assembly and disassembly at the ends of a microtubule.

 The microtubule can dynamically switch between growing and shrinking phases

22
Q

DYNAMIC INSTABILITY

Dynamics are influenced by the ? and ? of GTP which occurs only within the alpha or beta?-
subunit of the tubulin ?:

  • The addition of GTP - containing ?, to the end of a ? causes the end to ?
  • If GTP hydrolysis proceeds more rapidly than the addition of new subunits, the microtubule begins to shrink or grow?
A

DYNAMIC INSTABILITY

Dynamics are influenced by the addition and hydrolysis of GTP which occurs only within the alpha or beta subunits of the tubulin dimer:

  • The addition of GTP - containing tubulin, to the end of a protofilament causes the end to grow
  • If GTP hydrolysis proceeds more rapidly than the addition of new subunits, the microtubule begins to shrink
23
Q

MICROTUBULES- MAPs

Microtubule-associated ? (MAPs) move along ? bringing transport vesicles to target organelles in the cell:

  • ?, travels (normally) towards (+) end
  • ?, travels towards (-) end

ATP hydrolysis occurs in the ?

 Generates movement along the microtubule via the microtubule-binding domains

Dynein is composed of two identical ? chains, which make up two large ? head domains, and a variable number of ? and ? chains.
 Transport of intracellular cargos towards the + or - end of the microtubule?

Kinesin has a ? structure to dynein.
 Transport of a variety of intracellular ?, including vesicles, organelles, protein complexes, and mRNAs toward the microtubule’s (+ or -) end

A

MICROTUBULES- MAPs

Microtubule-associated proteins (MAPs) move along microtubules bringing transport vesicles to target organelles in the cell:

  • Kinesin, travels (normally) towards (+) end
  • Dynein, travels towards (-) end

(pic: atp bind to the myosin heads (which are ATPaes) and then they walk on the microtubules

ATP hydrolysis occurs in the globular head domains

 Generates movement along the microtubule via the microtubule-binding domains

Dynein is composed of two identical heavy chains, which make up two large globular head domains, and a variable number of intermediate and light chains.
 Transport of intracellular cargos towards the (-) end of the microtubule

Kinesin has a similar structure to dynein.
 Transport of a variety of intracellular cargoes, including vesicles, organelles, protein complexes, and mRNAs toward the microtubule’s (+) end

24
Q

MICROTUBULES -MAPs

The selective stabilization of the microtubules can ? a cell
 MAPs (microtubule-associated proteins) can move ? and ? within the cell

Cell polarity refers to ? differences in ?, ?, and ? within a cell.​

MICROTUBULES
MAPs can move vesicles with ? (melanosomes) in the skin

(melanin: pigment can be of diff. colors so animals that are rlly good at camoflage - have good VARIETY of melanin and melanosomes will be travelling at microtubules (..dimer?)

changes color quickly, so travels REALLY FAST on microtubles (millisenconds))

MICROTUBULES - MTOC
Microtubules originate from a specific cellular location known as ? (short form?)
* In animal cells, the ? is the major MTOC

Centrosome: made up of 2 cylinders called ?
Centrioles - very small cylindrical organelle near the ? in animal cells, occurring in ? and involved in the development of ? fibers in cell division.
(The centrosome is the whole thing and centrioles present in it)

A

MICROTUBULES -MAPs

The selective stabilization of the microtubules can polarize a cell
 MAPs (microtubule-associated proteins) can move organelles and vesicles within the cell

Cell polarity refers to spatial differences in shape, structure, and function within a cell.​

MICROTUBULES - MTOC
Microtubules originate from a specific cellular location known as microtubule organizing center (short form = MTOC)
* In animal cells, the centrosome is the major MTOC

Centrosome: made up of 2 cylinders called centrioles
Centrioles - very small cylindrical organelle near the nucleus in animal cells, occurring in pairs and involved in the development of spindle fibers in cell division.
(The centrosome is the whole thing and centrioles present in it)

25
Q

MICROTUBULES - MTOC

  • When a cell divides, the ?, which is responsible for aligning and segregating the chromosomes
     ? microtubuli
  • After division is complete, both daughter cells reorganize their ? and ?

MICROTUBULES – Cilia and Flagella

Microtubules have major structural role in eukaryotic ? and ? (highly specialized and efficient motility structures)
Always extend directly from a ? (basal body 9:2 structure)

Action of dynein motor proteins (along MT strands along cilium/flagellum) allow for ? and ? for movement.
 Prokaryotes possess ?-like proteins like eukaryotes, BUT prokaryotic flagella are totally different in structure from eukaryotic flagella, do not contain ?

A

MICROTUBULES - MTOC

  • When a cell divides, the MT rearrange to form a bipolar mitotic spindle, which is responsible for aligning and segregating the chromosomes
     astral microtubuli
  • After division is complete, both daughter cells reorganize their MT and actin filaments

MICROTUBULES – Cilia and Flagella

Microtubules have major structural role in eukaryotic cilia and flagella (highly specialized and efficient motility structures)
Always extend directly from a MTOC (basal body 9:2 structure)

Action of dynein motor proteins (along MT strands along cilium/flagellum) allow for bending and generating force for movement.
 Prokaryotes possess tubulin-like proteins like eukaryotes, BUT prokaryotic flagella are totally different in structure from eukaryotic flagella, do not contain MT based structures.

26
Q

MICROTUBULES – Cilia and Flagella

Flagella: are used to move cells in an ? environment e.g. ?

Cilia: can move fluid ? (e.g. ? in the respiratory epithelium)

MICROTUBULE SPECIFIC DRUGS

taxol: ? and ? microtubules
colchicine, colcemid: binds ? and ? their polymerization
vinblastine: same function as colchicine
nocodazole: same function as colchicine

A

MICROTUBULES – Cilia and Flagella

Flagella: are used to move cells in an aqueous environment e.g. spermatozoids

Cilia: can move fluid around a cell (e.g. mucus in the respiratory epithelium)

MICROTUBULE SPECIFIC DRUGS

taxol: binds and stabilizes microtubules
colchicine, colcemid: binds subunits and prevents their polymerization
vinblastine: same function as colchicine
nocodazole: same function as colchicine

27
Q

MICROTUBULES

PACLITAXEL/TAXOL
- ? chemotherapy: blocking ? to kill cancer cells
- cytostatic drug used in cancer therapy (breast/ovarian cancer) : inhibits progression of mitotic cells to G1 phase by interference with ? without affecting other microtubule functions during ? and ?

VINCA ALKALOIDS (vinca rosae, vinca minor)

Vincristine binds ? to ? and spindle proteins in S phase of the cell cycle and interferes with the formation of the ?, thereby arresting ? cells in ?.

Vinca alkaloids:
- alkaloids of the periwinkles -> vinblastin, vincristin, vindesin
- binds free tubulin -> prevents MT polymerization and cell division
- cytostatic (Leukemia, lymphoma, breast cancer)

A

MICROTUBULES

TAXOL/ PACLITAXEL
- anticancer chemotherapy: blocking microtubules to kill cancer cells
- cytostatic drug used in cancer therapy (breast/ovarian cancer) : inhibits progression of mitotic cells to G1 phase by interference with spindle formation without affecting other microtubule functions during anaphase and telophase

VINCA ALKALOIDS (vinca rosae, vinca minor)

Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase.

Vinca alkaloids:
- alkaloids of the periwinkles -> vinblastin, vincristin, vindesin
- binds free tubulin -> prevents MT polymerization and cell division
- cytostatic (Leukemia, lymphoma, breast cancer)

28
Q

MICROTUBULES

COLCHICINE
- Alkaloid of the autumn crocus (Colchicum autumnale)
- binds free tubulin -> prevents ? and ?
- anti- ? effects

INTERMEDIATE FILAMENTS
* No ? → so no ? or ? end
* Subunits don’t contain ? or ?
* Not involved in ?
* No ? associated

However… ? are associated with ? junctions, ? cells and epithelia, tissue ? stability

A

MICROTUBULES

COLCHICINE
- Alkaloid of the autumn crocus (Colchicum autumnale)
- binds free tubulin -> prevents MT polymerization and cell division
- anti-inflammatory effects

INTERMEDIATE FILAMENTS
* No polarity → so no + or - end
* Subunits don’t contain ATP or GTP
* Not involved in cell movement
* No motor proteins associated

However… intermediate filaments are associated with cell-cell junctions, strengthening cells and epithelia, tissue mechanical stability

29
Q

INTERMEDIATE FILAMENTS

  • Line the inner face of the ? envelope, forming a ? cage for the cell’s DNA.
  • In the ?, they are twisted into strong cables that can hold ? cells sheets together
  • Help ? cells to extend long and robust axons
  • Part of ? and ? structure (main intermediate filament here is keratin)

Intermediate’s central building block:
 2 ? proteins = ‘coiled-coil’ dimer
 Bound together by ? interactions

In a final IF there are #? dimers of IF monomers (=32 coiled coils)

A

INTERMEDIATE FILAMENTS

  • Line the inner face of the nuclear envelope, forming a protective cage for the cell’s DNA.
  • In the cytosol, they are twisted into strong cables that can hold epithelial cells sheets together
  • Help nerve cells to extend long and robust axons
  • Part of hair and fingernail structure (main intermediate filament here is keratin)

Intermediate’s central building block:
 2 intertwined proteins = ‘coiled-coil’ dimer
 Bound together by hydrophobic interactions

In a final IF there are 16 dimers of IF monomers (=32 coiled coils; 16 * 2 = 32)

30
Q

INTERMEDIATE FILAMENTS

EPITHELIAL KERATIN FILAMENTS:
* Most ? intermediate filament family
* Produced by ? in the epidermis
* Formation of ?, nails, hair, ?
* Anchoring of epithelial cells via ?/?

The diversity of keratins is clinically useful in the diagnosis of epithelial ? (carcinoma)

 Particular set of keratin filaments expressed gives an indication of the ? in which the cancer originated and thus can help guide the choice of ?

Mutation in keratin genes cause several ? diseases

A

INTERMEDIATE FILAMENTS

EPITHELIAL KERATIN FILAMENTS:
* Most diverse intermediate filament family
* Produced by keratinocytes in the epidermis
* Formation of horns, nails, hair, scales
* Anchoring of epithelial cells via desmosomes/hemidesmosomes

The diversity of keratins is clinically useful in the diagnosis of epithelial cancers (carcinoma)

 Particular set of keratin filaments expressed gives an indication of the epithelial tissue in which the cancer originated and thus can help guide the choice of treatment

Mutation in keratin genes cause several genetic diseases

31
Q

Intermediate filaments

In diseases where the gene coding for keratin is ?, the final protein disrupts the normal ? network in the ? cells of the skin and the epidermis can easily be detached (blistering)
* E.g. epidermolysis bullosa simplex (EBS)

INTERMEDIATE FILAMENTS
Other intermediate filaments
 ?: high concentrations along the axons of vertebrate neurons
* Participate in axonal growth (length and diameter)
* Provide strength and stability to the axon

 ?: mechanical stability of cell nucleus
 ?: scaffold function for sarcomere (skeletal and cardiac muscle)

A

Intermediate filaments

In diseases where the gene coding for keratin is mutated, the final protein disrupts the normal keratin network in the basal cells of the skin and the epidermis can easily be detached (blistering)
* E.g. epidermolysis bullosa simplex (EBS)

INTERMEDIATE FILAMENTS
Other intermediate filaments
 neurofilaments: high concentrations along the axons of vertebrate neurons
* Participate in axonal growth (length and diameter)
* Provide strength and stability to the axon

 Lamin: mechanical stability of cell nucleus
 Desmin: scaffold function for sarcomere (skeletal and cardiac muscle)