Cell Bio Flashcards
Define zonula occludens and its functions
Tight junctions
maintains polarity and forms a paracellular barrier
Proteins Occludens, and Claudins
Define zoluna adherens and its functions
Transmembrane cadherin proteins that connect cells extracellularly and also to actin filaments within each cell
Mechanical connection between cells
Define macula adherens and its functions
intracellular plaque-like proteins that connect cells extracellularly via complementary cadherin proteins
associates with intermediate keratin filaments
Define gap junctions and its functions
connexons that create channels between two cells for rapid transfer of ions and small molecules, as well as electrical and metabolic coupling
Connects two cells cytoplasm’s
What is a connexon and what is it composed of?
a gap junction protein, composed of a concentration of connexin proteins
What is the function of a hemidesmosome?
Anchors a cell to the basal lamina
similar to desmosomes but attach to integrin proteins as opposed to keratin filaments
What are some functions of the cytoskeleton?
Cell and organelle movement Phagocytosis and cytokinesis Cell-cell and cell-matrix connection Cellular strength and support Changes in cell shape
Describe intermediate filaments and their functions
ropelike fibers
provide structural support and cell attachment sites (Desmosomes)
Describe microfilaments and their function
double-stranded, helical actin structures
provide structure and is involved in cellular movement (microvilli mvmt, Actin and myosin motor protein movement)
Describe microtubules and their function
Hollow cylinders of tubulin proteins
Polymerization and depolymerization control movement of vesicles and organelles
Describe the makeup and function of cilia
Motile processes on cell surface in respiratory and reproductive epithelium
Comprised of microtubules in a 9+2 arrangement
Connects to an intracellular basal body also comprised of microtubules
Describe the composition and function of microvilli
Increases absorptive surface area
Actin core that connects to intracellular actin network
What process leads to the breakdown of the nuclear envelope?
Phosphorylation of nuclear lamina
What is the nuclear lamina?
Network of intermediate filaments adjacent to the inner membrane of the nucleus
Describe the process of large molecules passing through nuclear pores
prospective nuclear protein binds to a nuclear protein importer
this complex is guided to a nuclear pore via fibrils which extend from the outer membrane adjacent to the nuc. pore
active transport is required to bring the complex into the nucleus
requires a nuclear localization signal (7 AA’s)
Describe the process of detoxification by peroxisomes
Oxidase removes H atoms via O2 molecules to form hydrogen peroxide (H202)
Catalase uses the free radical H2O2 to oxidize other substances
- Zellweger Syndrome: Unable to recognize the 3AA sequence on peroxisome enzymes
What are the four cell fates?
- Survival (senescence) : Multiple distinct signals are required for cell to survive
- Division : Need survival signals but also signals that drive activation of cell cycle machinery and cell division (Most cancers disrupt these signals)
- Differentiation :Survival signals + new signals involving coordination of cell cycle exit and expression of distinct genes responsible for diff Phenotype
- Apoptosis: Self propagated suicide (Why we lose webbed fingers)
Stem Cells
Undifferentiated cell, immortal, can replicate and divide indefinitely. Divide and send one cell down the path of differentiation
Describe motor protein movement across microtubules. What proteins are involved and in what direction do they move?
Microtube has minus end (centromere) and plus end
Plus end can grow, minus end can shrink
Dynein moves to the plus end
Kinesin moves to the minus end
Nucleolus
Site of rRNA synthesis, contains multiple loops of DNA coding rRNA genes.
Ribosomal subunits are made in the nucleus but come together in the cytosol
Describe the structure of cilia/flagella
Axoneme - inner core of cilia/flagella
Microtubules and dynenin arrange in 9 pair + 2 formation
Stabilized by nexin and radial spokes
What are the three modes of transport of a cytosolic protein?
Gated-transport - transported through a gated membrane protein (nuclear pore)
Transmembrane transport - cytosolic protein moves across membrane via a specific transmembrane protein
Vesicular transport
Heat Shock Proteins
Chaperones.
Nuclear mitochondria proteins use heat shock proteins to be transport into Mitochondria
Three pathways from the Golgie
- Exocytosis (default): to plasma membrane
- Secretory granules: vesicles accumulate secretory product and await stimulus
- Lysosomes: Vesicle fusion with late Endosomes
Lysosome Maturation
- Early Endosome - Found close to the membrane
- Late Endosome - found closer to Golgi and is lower in pH than the early endosome due to proton pumps accumulated from Golgi
- Lysosome: Late endosome that fuses with vesicles from Golgi containing acid hydrolase
- Residual (Inclusion) bodies - product after digestion, containing undigested material
Two pathways of Exocytosis
Constitutive secretion: (Default) Continuous secretion
Regulated secretion: Molecule’s stored in storage granules, use clathrin coated vesicle and are released after specific stimuli
- Which cell fate is most surprising from an evo perspective?
- Which cell fate(s) is suppressed for terminal differentiation?
- Which cell fate(s) are generally not applicable to stem cells?
- What is fate of liver cells upon ingestion of amatoxin?- A child is born with webbed fingers, which cell fate was disrupted?
- Apoptosis
- Proliferation and Apoptosis
- Stem cells don’t senesce or differentiate
- Apoptosis
- Apoptosis
What are some functions of the smooth ER?
Synthesis of steroids
Sequesters calclium
detoxifies toxic, insoluble compounds
Rheb
- GTPase switch (Rheb hydrolyzes GTP>GDP and becomes inactive)
- Causes cell proliferation so needs to be regulated to prevent cancer
- GAP: GTPase Activating Protein (Causes the hydrolyzation of GTP and shuts off Rheb)
- GEF : Guanine Exchange factor Exchanges GDP>GTP turns on GTPase
- Signaling specificity is achieve mainly at the level of ?
- What is the major process driving cell cycle differentiation?
- Gene expression changes are most directly mediated by?
- The GAPs regulate Rheb by?
- Leukemias can result in excess but nonfunctional blood cells. Which cell fate is affected?
- Ligand binding
- Gene expression
- Specific transcription factors
- GAPs activate GTPases turning them off
- Differentiation (???)
Cell Cycle Stages
- G1: Longest period of cell cycle in which cell grows and evaluates external signals to decide what to do
- G0: Cell exiting cell cycle to adopt a new fate
- R site: where decision of cell fate is made
- S phase: Synthesis phases, DNA replicated completely and accurately as possible
- G2: DNA replication is evaluated and preparations for M phase are made
M phase: Mitosis
Cyclin Dependent Kinases (CDKs)
Drive cell cycle transitions
CDKs activated by binding to different cyclins that are only expressed at random times of the cell cycle
Required order of cycle progression achieved by ordered expression and activation of specific cyclin-CDK complex
CDK Cascade
Highly regulated by positive and negative events
- CDK binds to Cyclin becoming partially active
- Cyc-CDK gets phosphorylated by CAK -> Activated
Inhibition
INK4 Inhibits CDK and Cyc-CDK
CIP inhibits Cyc-CDK, Cyc-CDK +CAK, And Cyc-CDK-P
CDKs regulate transcription by removing Rb off of transcription factors (Rb is transcription inhibitor)
Growth Factor
- activating cell proliferation pathways
- activate Ras/Raf/ERK pathways
- Ras activate Cyclin D and inactive CDK inhibitors driving progression through G1
- Ras is QUINTESSENTIAL GTPase switch (can lead to unstable proliferation
- Controlled by GAPs and GEFs
- What is order of cell cycle phases?
- CDKs catalyze what reaction?
- Cyclin levels are mainly controlled by?
- Ras is?
- HPV can cause cervical cancer by infecting epithelial cells. What epithelial cell fate is affected?
- M, G1 (G0), S, G2
- Phosphorylation
- Transcription + Degradation
- Enzyme
- cancer effects proliferation
When and how is p53 activated and what downstream cell fates can occur?
DNA damage signals at restriction check point result in kinase mediators phosphorylating and activating p53
p53 initiates cell cycle rest for DNA repair/apoptosis
Restriction point
Where cell fates are made
Activate G1 CDKs to continue cycle to become mitogen independent or inhibit G1 CDKs to exit and adopt an alternate fate
G1 progression
Switch to mitogen independence- Generate D-K4 that phosphorylate and inactivates Rb releasing E2F which transcriptionally activates Cyclin E
Cyclin E has a positive feedback loop making more Cyclin E and thus inhibiting Rb more and more
- Where is R point located
- The R point is involved in?
- What is substrate of Cyclin D-CD4?
- Cyclin E-CDK2 is part of a positive feedback loop controlling what activity?
- 100 mil bacteria must be injested to cause cholera. The # is lower for ppl taking antacids. What bacterial cell fate is being enhanced by antacids?
- After G1
- Fate decisions
- Rb
- Rb
- Survival
Three Checkpoints monitoring cell cycle progression
- M phase: Spindle Assembly Checkpoint: check for chromosome attachment to spindle
- R point: Restriction checkpoint: Cell size, nutrients, GFs, DNA damage
- G2: check for cell size and DNA replication
Intracrine signalling
signal produced within targeted cell
Juxtacrine signalling
Direct contact signalling (cell-cell contact, synapses, gap junctions)
eg. notch pathway
Autocrine signalling
signal is excreted and targets same cell
e.g. Hormones, Growth Factors
Paracrine signalling
short distances (adjacent cells)
Endocrine signalling
large distances (blood stream/lymph)
Contrast transport of hydrophobic and hydrophillic signal molecules
Hydrophobic - require carrier protein for transport to target cell
diffuse through cell membrane
Require intracellular receptor
Hydrophillic - require extracellular receptor and transport across membrane
What are defining characteristics of nuclear hormones?
Activity is in nucleus
Hydrophobic, require transport proteins
Persistent in blood stream (hours/days)
eg.steroids, vitamin A
Describe nuclear hormone regulation of protein synthesis
Nuclear hormone enters the cell and binds to heat shock protein
Nuclear hormone receptor binds ligand on its ligand-binding domain, releasing HSP
receptor enters nucleus and binds to DNA via its DNA-binding domain
Down or up-regulates transcription
Agonist
Binds a receptor to elicit a response
can be a synthetic hormone or naturally occurring hormone
cAMP signalling
G-protein coupled receptor activates adenylate cyclase, which converts ATP to cAMP
cAMP can activate protein kinase A which is involved in many cellular pathways
cAMP is eliminated by phophodiesterase
G proteins can also inhibit cAMP signalling
Antagonist
Binds to receptor to prevent function
Mifepristone/Ru-486 antagonist of progesterone used for medical abortions
Receptor tyrosine kinase (RTK)
Enzyme-linked cell surface receptor
Activated when ligand binds to extracellular domain, inducing dimerization of two RTK’s
dimerized RTK’s phosphorylatte intracellular tyrosine residues on each other’s intracellular domains
Activation of G-Protein
- Ligands binds to GPCR, G proteins takes up GTP (activated)
- alpha subunit will diffuse laterally to activate effectors
- Alpha converts GTP-> GDP stopping activity
- GAPs also help regulate
G proteins activate adenylate cyclase which makes secondary messenger -> cAMP
Overall: G protein stimulates Adenylate cyclase (can also inhibit) which converts ATP->cAMP
PIP2 Pathway (Phosphatidylinositol-4,5-bisphosphate)
Activated by G-protein
- GProtein activates phospholipase C by phosphorylation
- Phospholipase C cleaves PIP2 making IP3 and DAG
- DAG and the Ca2+ activate protein kinase C which can activate other pathways
What are characteristics of enzyme-linked cell surface receptors?
Have an extracellular ligand-binding domain
Transmembrane component
Intracellular domain w/ enzymatic activity or association with an enzyme
Ras Pathway
GTPase indirectly activated by receptor tyrosine kinase (RTK)
three types: H-, K-, and N-
Activated mitogen activated protein kinases (MAPKs)
Activated by GEF, inactivated by GAP
P13 kinase
P13K is activated via phosphorylation by RTK or Ras
P13K phosphorylates PIP2 to PIP3 which induces a growth and survival signal
PTEN dephosphorylates PIP3 back to PIP2
WNT Signaling
- WNT is a morphogen (governs tissue development) that binds to surface receptor
- Leads to inhibition of Adenomatous polyposis coli(APC) which is an inhibitor of beta-catenin)
- WNT –| APC –| B Catenin (WNT allows B-catenin to proliferate)
- Very common in Colon cancer, APC is mutated and cant phosphorylate B-catenin
