When did prokaryotes arise?
3.5 billion years ago
When did eukaryotes arise?
2.5 billion years ago
What is the first evidence of life? To how long ago does this bring us (2 types)?
Stromatolites in carbonate sediments 1. Archaea: 3.4-3.5 billion years ago 2. Proterozoic: 2.8-3 billion years ago (in rocks)
What are 2 another names for stromatolites?
What is the theory that explains how eukaryotes arose? What evidence do we have for this?
Archae were the host cells of bacteria (the formed an endosymbiotic relationship) Evidence: 1. Archae contain DNA w/ introns, promoters, histones, and transcriptional machinery similar to eukaryotes, which probably formed the eukaryotic nucleus 2. Archae glycosylate proteins and bacteria do not
What are metazoans?
Evolved versions of eukaryotes with cell junctions and connective tissue
When did metazoans arise?
850 million years ago
What is the homeotic gene family?
Genes which regulate the development of anatomical structures in various organisms
When did the homeotic gene family arise?
600 million years ago
What are the 3 domains of life?
1. Bacteria 2. Archaea 3. Eukarya
What was the first version of life? What are the 2 types?
Prokaryotes: unicellular without organelles 1. Bacteria 2. Archaea
Are all eukaryotes multicellular organisms?
What are the 3 types of eukaryotic multicellular organisms?
1. Animals 2. Plants 3. Fungi
What are extremophiles?
Subtype of archaea that thrives in extreme environments
What are thrombolites?
Fossils that appear in the early proterozoic and are related to stromatolites
What are oncolites?
Fossils that appear in the pre-Cambrian and are related to stromatolites and thrombolites
What are algal filament fossils?
Fossils that appear in chert (dark rock in the North Pole and Australia) and are evidence of life 3.5 billion years ago
What are spheroidal bacterial structures?
Prokarytic fossil evidence from 3 to 3.1 billion years ago found in South Africa
What are the surface mats of stromatolites?
Bicarbonate sediments that contain mainly cyanobacteria and have other eubacteria, archaebacteria and eukaryotes in close proximity
What do thrombolites and oncolites look like?
Very uniform rocks
What did the bacteria that fused with the archaea become in the eukaryotes? 2 options
1. Mitochondria 2. Chloroplasts
How did other organelles (other than mito) develop in eukaryotes?
Infolding of plasma around bunches of proteins and enzymes
What are the main roles of integral proteins?
Pores and receptors
What is the main role of peripheral proteins?
Accessory proteins for the integral ones
What is the glycocalyx?
All of the sugars attached to glycolipids on the exterior of the lipid bilayer
What is the E face of the lipid bilayer?
The external face of the internally fractured membrane
What is the P face of the lipid bilayer?
The protoplasmic (internal) face of the internally fractured membrane
What do prokaryotes have instead of a nucleus?
Nuclear organizing region, but it's not a distinct organelle
What are the 4 components of the nuclear membrane?
1. Inner membrane 2. Outer membrane 3. Cisterna (between the 2) 4. Nuclear pore complexes to regulate the mvt of macromolecules
What does the outer membrane of the nucleus sometimes contain? What does this mean?
Ribosomes, which means the nucleus is continuous with the RER
What kind of permeability does the nuclear envelop have?
What is the inner membrane of the nucleus associated with?
Nuclear lamina protein meshwork that binds to chromatin in non-dividing cells
What kind of filaments are the lamins of the nuclear membrane made of?
What do nucleoporins look like?
What are the 4 subunits of a nuclear pore? What 2 other parts are attached to it?
What is the whole thing called?
1. Luminal subunit 2. Ring subunit 3. Column subunit 4. Annular subunit Other parts: - Fibrils toward the cytosol - Nuclear cage toward the nucleus
How do nuclear pores work?
Translocating proteins have nuclear export or import localization sequences that bind specifically to transport proteins that in turn interact w/ proteins in the pore for transfer
What are the 2 types of transport proteins?
1. Importins 2. Exportins
What kind of molecules through a nuclear pore complex and through what transport mechanism?
1. Small ions and solutes (like H2O): simple diffusion w/o regulation 2. Macromolecules: active transport regulated by the pore
What molecules are transported out of the nucleus?
Ribosomal subunits and other RNA-associated proteins
What molecules are transported into nucleus?
Molecules for DNA replication and trancription: chromatins, ribosomal proteins, transcription factors, and enzymes
What is the nucleolus?
A subsection of the nucleus responsible for making ribosomal RNA (rRNA)
What does the nucleolus look like under a microscope? When can you observe it?
Darker region within the nucleus Resting state in interphase
What are the 3 parts of the nucleolus and what does each consist of?
1. Pars amorpha: DNA that codes for rRNA 2. Pars fibrosa: rRNA 3. Pars granulosa: maturing ribosomal subunits
What is another name for pars amorpha?
Nucleolar organizer region
What is the nucleolonema?
Pars fibrosa + pars granulosa
How to distinguish the different parts of the nucleolus looking through a microscope?
1. Pars amorpha: lighter circular part 2. Pars fibrosa: slightly darker around the pars amorpha 3. Pars granulosa: slightly darker but not around the pars amorpha
What happens to the nucleolus during the cell cycle?
It assembles and disassembles
What are the 2 forms of chromatin? Describe each
1. Hetero: heavy staining, highly condensed 2: Eu: light staining and uncoiled
What are the 2 components of chromatin?
2. Protein: histones and non-histone chromosal proteins (eg: transcription factors)
What is the nucleolus-associated chromatin? What kind of chromatin?
NAC: heterochromatin around the nucleolus
Describe each condensation step from the DNA double helix to the metaphase chromosome
1. DNA double helix 2. DNA w/ histones: nucleosomes (beads on a string) 3. Additional folding and packing: 30 nm chromatin fiber 4. Looped domains 5. Condensed chromosome 6. Metaphase chromosome
What 2 types of organisms have a larger genome than others?
1. Plants: because they are sedentary and need genes to help them survive (flooding, insects attacking, etc) 2. Amphibians: need more genes to help live in both terrestrial and aquatic environments
How many nucleotide pairs in the human genome?
Which type of chromatin is transcriptionally active?
What are the 2 cell division processes for eukaryotes?
1. Mitosis 2. Meiosis
What is the division process for prokaryotes?
What is the division process for mitochondria and chloroplasts?
What accounts for the large majority of genetic diversity?
What can explain why it took so long for eukaryotes to evolve?
Because genetic diversity was only possible through chemical mutagenesis, which is very slow vs meiosis which enables rapid evolution
Describe the cell cycle. How long does it last?
- G1: normal function (in this stage most of the time) and accumulation of enzymes and nucleotides - S phase: DNA duplication - G2: preparation for mitosis - M phase: mitosis 24 hours
What are the 6 phases of mitosis? How long does each last?
• Interphase: Growth period; cell carries out normal functions
• Prophase (1 hr): Nuclear membrane disappears, chromatin condenses into chromosomes and the centrosomes move to opposite poles of the cell, mitotic spindle forms
• Metaphase: Chromosomes further condense and align at the equatorial plane.
• Anaphase: Sister chromosomes move toward spindle poles.
• Telophase: Sister chromosomes arrive atthe poles.
• Cytokinesis: A cleavage furrow divides the cytoplasm and duplicated chromosomes into two daughter cells.
Describe the composition of ribosomes
Small and large subunit
What RNA do ribosomes bind?
What kind of proteins do free ribosomes synthesize?
Intracellular proteins: cytosolic and cytoskeletal proteins and proteins for import to the nucleus, the mitochondra or the peroxisomes
What kind of proteins do RER ribosomes synthesize?
Proteins that require further processing
Which types of proteins get more PTMs than others?
Those synthesized by the RER vs the free ribosomes
On what are ribosomes attached on the RER?
The cisternal membrane
What is a polysome or polyribosome?
Single mRNA molecule associated with a number of ribosomes along it
What happens to proteins after they are synthesized by ribosomes on the RER?
Often stored in lysosomes or secreted out
Describe the movement of nascent peptides from free ribosomes to RER the lumen
1. Nascent peptide's has a signal peptide that binds a signal-recognition particle which inhibits further elongation
2. SRP-peptide complex binds an SRP receptor on the ER membrane thanks to docking proteins
3. SRP releases the signal peptide for translation to continue
4. Protein translocators bing to the ribosome and form a channel for the peptide to go through the ER membrane: vectorial discharge
5. The peptide pushes itself and is pulled by chaperones
6. The signal peptide is removed inside the RER lumen
What does TEM stand for?
Transmission Electron Microscopy
What are the 5 functions of the ER?
1. Cleavage of signal-peptide
2. Protein folding
1. Breakdown of glycogen
2. Detoxification of drugs
3. Regulation of muscle contraction
4. Synthesizes phospholipids, fats, and steroids
What happens to the protein in the ER if it's not folding properly?
Ubiquitylated to be sent to the proteasome
What is Golgi apparatus ?
Stack of membranes that modifies, sorts, and packages proteins from th ER
What are the 2 faces of the Golgi?
1. Cis: forming: close to ER 2. Trans: secreting: where proteins are released near the plasma membrane
What are the 3 parts of the Golgi? What does each do?
1. cis Golgi network: phosphorylation of oligosaccharides on lysosomal proteins 2. Golgi stack (other slide) 3. trans Golgi network: addition of NANA and sorting (!!)
What are the 3 parts of the Golgi stack? What does each do?
1. Cis cisterna: removal of Man 2. Medial cisterna: removal of Man and addition of GlcNAc 3. Trans cisterna: addition of Gal
What is NANA?
What is GlcNAc?
What about the environment changes as a protein moves through the Golgi?
pH: decreases from cis to trans
How do proteins from the RER get to the Golgi?
What regulates the movement from the RER to the Golgi?
Coat protein-II (COP-II)
What happens to proteins in the Golgi that are misfolded?
Recognized by KDEL receptor proteins and sent back to the RER by COP-I for refolding or degradation
What happens to the proteins once they are secreted by the Golgi?
1. Directed to fuse with an late endosome to become a lysosome 2. Directed for secretion
What is the pH in lysosomes? How did scientists figure this out?
5 Using certain fluorescent dyes that change spectrum with pH
What is the cytoslic pH?
What type of enzyme are in the lysosomes? List some of these
Acid hydrolases: 1. Nucleases 2. Proteases 3. Glycosidases 4. Lipases 5. Phosphatases 6. Sulfatases 7. Phospholipases
How do lysosomes create that acid pH?
Proton pumps using ATP
What is necessary when primary lysosomes form secondary lysosomes?
Need to fuse with membrane bound organelles to maintain pH
What are the 4 types of secondary lysosomes and what do they correspond to?
1. Lysosome + phagocytosis vesicle = digestive vacuole 2/3. Lysosome + endocytosis vesicle = multivesicular body or generalized secondary lysosome 4. Lysosome + mitochondrion = autophagic vacuole
What is an endocytosis vesicle?
A vesicle that has taken in material from the cell surface
What is special about peroxisomes?
They are very primitive in date, appearance, and function
What is another name for peroxisomes?
Describe the composition of a peroxisome
Vesicular organelle composed of small packets of oxidative enzymes surrounded by a single membrane
How do peroxisomes grow?
Uptake of peroxisomal proteins from cytoplasm by specific proteins that catalyze the import
How do peroxisomes divide?
Cytoplasmic fission (no DNA involved)
What are the 3 functions of peroxisomes?
1. Oxidation of harmful substances via generation of H2O2 2. Detoxification of alcohol and other harmful chemicals 3. Beta-oxidation of long-chain fatty acids (first step of their breakdown)
What is the major function of peroxisome?
Oxidation of harmful substances via generation of H2O2
What is the rxn that happens in peroxisomes?
RH2 + O2 --> R + H2O2
Where are mitochondria found? Why?
On the cytoskeleton to be able to move
Describe the 6 parts of the mitochondria
1. Inner membrane 2. Outer membrane 3. Intermembrane space 4. Cristae: folds in inner membrane to increase surface area 5. Elementary particles on inside of inner membrane: proton pumps to facilitate ATP generation 6. Matrix: inside the inner membrane
What is another name for elementary particles?
What gave rise to mitochondria? What are the 4 pieces of evidence
Endosymbiosis of aerobic bacteria: 1. Mito has its own circular chromosome of DNA, ribosomes, mRNA, tRNA (just like bacteria) 2. Undergo fission (like prokaryotes) 3. Double membrane: outer from ancestral host and inner from symbiotic prokaryote 4. Closest genotypic relatives of mitos are rickettsia bacteria: intracellular parasites of eukaryotic cells
Explain mitochondrial inheritance
Maternal because very few paternal mitos can survive the fertilization process
What is the mitochondrial eve? How long ago did it exist?
The matrilineal most recent common ancestor of all humans, which lived about 200 K years ago
Descrive mito DNA
37 genes = 16,000 base pairs
How do the mito proton pumps generate ATP?
Flow of H+ down their electrical gradient creates mechanical rotational energy (of specific proteins) which is then converted into chemical energy to bind ADP and Pi = oxidative phosphorylation = chemiosmotic mechanism
When does mitos synthesize ATP the most?
During aerobic respiration
What does the matrix of the mito contain? 2 types
1. Metabolic enzymes for the TCA 2. Materials necessary for protein synthesis: DNA, mRNA, tRNA, ribosomes, and dense granules of precipitated salts
How does the mito get H+ inside its inner membrane?
Pumps because the membrane is impermeable to them
Is there a lot of genetic diversity in mDNA?
NOPE because of binary fission (instead of meiosis)
Are all of the proteins needed by the mito coded for in the mDNA?
List the 3 types of cytoplasmic inclusions
1. Pigment granules 2. Glycogen 3. Lipid
Are glycogen and lipids membrane bound in the cytoplasm?
Nope but they are round to minimize surface tension
What are the 2 types of pigment granules?
1. Melanosomes: contain melanin 2. Lipofuscin: contain residues of lysosomal digestion
Are pigment granules membrane enclosed?
What are 2 other names for lipofuscin?
1. Residual body 2. Tertiary lysosome
What is glycogenolysis?
Degradation of glycogen to produce glucose
What are the 3 parts of the cytoskeleton (from smallest to largest)?
1. Microfilaments 2. Microtubules 3. Intermediate filaments
Where are melanosomes found?
Epidermis and inner pigmented layer of the non-neural retina
What organelle fills up almost the entire interior of the cell?
What are microfilaments?
Helical chains of actin
What are the 2 types of actin?
1. Filamentous actin = F actin 2. Globular/monomeric actin = G actin
Describe the composition of actin fibers. When do they assemble?
Globular monomers that assemble in the presence of K+ and Mg2+ into double-stranded helices of filamentous actin
How is F actin elongated/shortened? How fast does this happen?
- Elongated: monomers are added at the + end - Shortened: monomers are removed from - end Rapid!
What are 4 functions of actin?
1. Intracellular mvt 2. Muscle contraction 3. Membrane structures 4. Locomotion
What are the 2 models of intracellular movement? Explain each
1. Cortical Flow Model: cell mvts controlled by the flow of actin filaments into the cell cortex governed by gradients of tension in the cortex generated by myosin (from low tension to high tension) 2. Leading Edge Model: actin at the leading edge of the migrating cell undergoes rapid remodeling
What does the Cortical Flow Model of intracellular movement account for?
Cytokinesis: cells divide due to high tension in the equatorial midline of the cell creating a cleavage furrow
How does actin contribute to cell motility and contractibility (shape) of the cell?
Actin attaches and forms stress fibers
How does actin contribute to cell structure? 2 ways
1. The filaments form the terminal web attached to zonula adherens under the apical cytoplasm 2. Filaments in microvilli and stereocilia (different from cilia) anchor into the terminal web
How does actin contribute to cell locomotion?
Actin filled filopodia (look like fingers) on cells to move them around, sense their surroundings, and interact with other cells
Describe the composition of microtubules
Heterodimer of alpha and beta subunits (tubulin) form a hollow slight spiral organization and polarity
What are the 3 types of microtubules?
1. Individual fibers: mitosis spindles or axons of neurons 2. Doublets w/ other proteins = axoneme: cilia core (flagella) and sperm tail 3. Triplets: centrioles
How are microtubules elongated/shortened? How fast does this happen?
- Elongated: free tubulin dimers are added (fast)
- Shortened: dimers are removed (slow)
What is a centrosome?
Two orthogonal centrioles (triplets of microtubules) which are the nucleating sites for polymerization of microtubules
What is another name for a centrosome in a mitotic cell?
Microtubule organizing center (MTOC)
What is a basal body?
A centriole (doublet of microtubules) that nucleates the axoneme of cilia
What are the 2 types of cilia?
1. Motile: axoneme with a central doublet of microtubles 2. Primary: axoneme lacking a central doublet of microtubules which are non-motile but have a sensory function
How many primary cilia do most cells have?
What's the relationship between intermediate filaments and tumors?
Keratins have 30+ isoforms and can be used to grade a tumor (gage degree of transformation)
What are the 4 types of intermediate filaments?
1. Nuclear lamins 2. Vimentinlike proteins 3. Keratins 4. Nuclear intermediate filaments
What are the component polypeptides of nuclear lamins? Where are nuclear lamins found?
Lamins A, B, and C Nuclear lamina
What are the 4 possible components of vimentinlike proteins and where is each found?
1. Vimentin: many cells of mesenchymal origin 2. Desmin: muscle 3. Glial fibrillary acidic protein: glial cells 4. Peripherin: neurons
What are the 2 types of keratins and where are they found?
1. Type 1: acidic 2. Type 2: Neutral/basic Epithelial cells and their derivatives
What is the role of keratins for terrestrial vertebrates?
They accumulate to provide a barrier to reduce dehydration and protect from pathogens
What is the role of keratins?
Attach to the desmosomes in the cytoplasm to form a framework
What are the 4 types of cell junctions?
1. Zonula occludens (tight junctions) 2. Zonula adherens (intermediate junctions) 3. Macula adherens (desmosomes) 4. Communicating (gap) junctions
What is the basolateral portion of the cell?
The one toward the ECM = interstitial space
What is the apical portion of the cell?
The one toward the lumen
Describe zonula occludens (tight junctions). What do they maintain? With what proteins do they do this?
Band encircling the apical end of a cell to prevent mvt of molecules between the lumen and the interstitial space (therefore solutes need to go through cells) This maintains cell polarity and forms a seal between neighboring cell membranes due to interactions between transmembrane proteins: claudin and occludin
Describe zonula adherens (intermediate junctions)
Anchor cells to each other:
Encircle epithelial cells right below the zonula occludens by using cadherins bound to catenin bound to actin like filaments (form the terminal web that help anchor actin filaments originating from microvilli at the apical end of cells)
Describe the 2 types of macula adherens (desmosomes)
1. Full one: spot welds around the cell perimeter (lateral sides) to attach cells together 2. Hemi: anchors the basal lamina of the basement membrane
What are the 2 parts of the basement membrane?
basal lamina + lamina reticularis
What is a desmosome composed of?
Transmembrane proteins of the cadherin family: (desmoglein and desmocollin) insert into a dense attachment plaque made of anchoring proteins inside the cell (plakoglobin and desmoplakin) which attach to keratin inside the cells
What's the difference between the protein composition of desmosomes and hemidesmosomes?
Integrins replace cadherins in hemidesmosomes
What is the role of communicating/gap junctions
Mediate rapid communication between cells by letting small molecules pass through channels(<1.5 nm) (ions, sugars, amino acids)
What are the small molecules that can go through gap junctions?
Ions, sugars, AAs (hydrophilic molecules)
What is a type of coordinated function allowed by gap junctions?
What proteins are gap junctions made of?
6 connexins = 1 connexon 2 connexons = channel with a hydrophilic core
What is a nucleosome?
DNA + histones = beads on a string
What is sialic acid?
N-acetylneuraminic acid!!!! NANA
What is the transitional ER?
A specialized region of the ER which is free of ribosomes and contains vesicles to take the proteins away
What is the cisternal maturation model?
New cis cisternae continually form and migrate to the trans face in the Golgi
What are condensing vacuoles?
Vacuoles in the trans Golgi network to become transport vesicles
What is the enzyme catalase used in? For?
Used in peroxisomes to use H2O2 to oxidize various substances
What is dynein?
Protein associated with individual microtubules in an axoneme that allow for ciliary movement by hydrolyzing ATP to generate a sliding force between 2 microtubule doublets
What is myosin? What are the 2 types?
Family of proteins that interact with actin to produce tension
1. Type 1: present in non-muscle cells and responsible for mvt of organelles along actin filaments
2. Type 2: present in muscle and non-muscle cells and contains a globular head that can bind actin and a fibrous tail that can form polymers
What is the cell cortex?
Layer of actin right beneath the plasma membrane of many cells and gives mechanical strength to the cell surface and enables it to change shape and to move
What are the 4 molecules that mediate cell adhesion?
2. Ig (embryogenesis, healing, and inflammatory response)
4. Selectins (bind to carbs)
4. Cadherins (Ca2+ dependent)