Term
| Two main clases of signal transduction |
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Definition
1) Membrane protein receptors: have to activate other factors to affect gene transcription
2) Nuclear receptors: bind to steroid hormones that directly affect gene transcription |
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Term
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Definition
Autocrine: cells signal themselves
Paracrine: Short range cell signaling
Juxtacrine: Signaling the cell next door
Endocrine: Signaling throughout the entire organism, may be used as a general term for any of the signaling mechanisms. |
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Term
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Definition
-A major class of transmembrane signaling proteins
-Always active
-The must dimerize to have their affect
-They trans-phosphorylate eachother
-This allows SH2 proteins to bind to the receptor |
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Term
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Definition
-Grb2-->SOS-->Ras-->Raf-->Mek-->ERK
-Use signaling cascades and scaffolding proteins
-SOS can activate lots of Ras |
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Term
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Definition
Signaling proteins are recruited to the receptor that eventually act on the nucleus as the transcription factors.
-This is much more direct than RTKs and does not use a cascade. |
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Term
| Cell Membrane organization |
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Definition
-Many different lipid types
-LIpids can differ in head, tail, or modifications
-Inner leaflet can't change to outer leaflet with out the help of a flippase |
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Term
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Definition
-Can make up to 80% of the membrane
-Many varieties of lipid modifications on the inner side
-GPI anchor is the only lipid modification on the outer side |
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Term
| The Dynamic Boundary Model |
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Definition
| -Membrane proteins are limited in their movement by either structural barriers (proteins) or phase boundaries (lipids) |
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Term
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Definition
-Also called membrane microdomains
-Similar lipids will aggregate together and create environments that will favor some proteins over others. |
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Term
Membrane Skeleton System
Triangles? |
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Definition
-Simplest version is when a transmembrane protein attaches to the cytoskeleton via adaptor proteins
-Spectrin proteins dimerize and connect the ends of triangles via actin and the junctional complex |
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Term
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Definition
-Three G proteins are bound to a receptor
-Ga is a GTPase, Gb is a GEF that activates Ga
-When Ga gets activated the G's will activate Phospholipase C, B gets released and causes IP3 to release its Ca stores.
-Ca and a lipid tail from PLC then bind to protein kinase C |
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Term
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Definition
-When in the GTP bound state G-alpha can activate adenyl cyclase and turn ATP into cyclic AMP
-cAMP can then activate PKA
-PKA can then enter the nucleus and phosphorylate |
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Term
| The many roles of actin (6) |
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Definition
-Cell Structure
-Cell migration and motility
-Cell adhesion
-Tension forces
-Endocytosis
-Cell division |
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Term
| Possible forms of actin and microtubules |
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Definition
Actin: branched/cross-linked meshwork, thick cables, individual, higher order structures
Microtubules: bundles and anchoring, no branching or meshwork. |
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Term
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Definition
-F actin: filaments, G-actin: monomers
-Nucleation: formation of a tetramer, slow, allows control of process
-Polymerization: short filaments made longer |
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Term
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Definition
-Nucleation prevented by profilin and thymosin
-CapZ caps the barbed end to prevent adding on
-Concentration drives formation of G and F actin |
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Term
| How to produce more actin barbed ends |
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Definition
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Term
| Actin filament nucleation systems |
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Definition
-Formins/Spire/Vast: sticks monomers together, hangs around to add more to the barbed end and prevent capping
-Arp2/3: branches |
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Term
| What types of cells are microtubules found in? |
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Definition
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Term
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Definition
-Made up of alpha and beta dimers (both exist almost always in dimers)
-A strand is called a protofilament
-beta is the end and alpha is the - end |
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Term
| similarities and differences between actin and microtubles |
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Definition
similar: polarized, extend from end in cells
different: microtubules are less stiff, exhibit dynamic instability, have less treadmilling, bind GTP/GDP |
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Term
| What is the role of gamma tubulin? |
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Definition
-It controls the nucleation of a/B tubulin.
-Not required for polymerization
-Found in the MTOC
-Tethers tubulin to the MTOC |
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Term
| What is the purpose of the MTOC? |
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Definition
The microtubule organizing center captures mt by their - end. The MTOC contains gamma-tubulin
-They also contain two centrioles |
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Term
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Definition
-Tubulins are GTPases with GEFS. GTP-Tubulin is only added on the end.
-The GTP is hydrolyzed spontaneously, so if no new tubulin is added then the microtubule undergoes catastrophe
-Returning the cap and initiating polymerization is called rescue. |
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Term
| Why are there so many types of motor proteins? |
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Definition
| -They have a wide range of function. |
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Term
| 3 ways to classify motor proteins |
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Definition
1) The type of track used- actin or microtubule
2) Direction
3) Duty cycle- processive or not |
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Term
| Motor track classification |
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Definition
-Actin: myosin fam, found in every cell type, contractibility, tension, cell morphology, migration, cytokinesis
-Microtubule: Dynein (toward - end), kinesin (toward end), in all cells, vesicle transport, cilia movement |
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Term
| Motor classification via movement |
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Definition
-ATP hydrolysis is required at the head domain
-Cargo is packed onto the tail
-Kinesin is smaller, towards end
-Dynein is huge, towards - end |
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Term
| Facilitating a motor step |
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Definition
-Binding ATP picks up the foot
-Hydrolyzing ATP cocks the foot
-Taking off the phosph puts the foot down
-Letting go of ADP causes the power stroke |
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Term
| Processive vs. non-processive |
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Definition
-Processive motors work w/a repetitive duty cycle, they coordinate movement along the entire track
-Non-processive-one legged myosins, can only move cargo a small distance, a vesicle may have many motors on it |
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Term
| Examples of cell adhesion |
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Definition
-Cadherin: cell to cell
-Integrin: cell to substrate
-Both together allow for complex cell arrangements |
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Term
| How cell adhesions work in general |
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Definition
-Adhesion receptors bind to adhesion targets outside the cell, and to adapter proteins inside the cell
-Adaptor proteins then link the adhesion system to cytoskeletal components, providing strength |
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Term
| Why are there many cadherin types? |
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Definition
| -To allow for different cells to adhere with specificity |
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Term
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Definition
-Cells with cadherins will aggregate
-If the cells are expressing different cadherins, then they will aggregate in layers. |
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Term
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Definition
-Laterally associates with cadherins to form specialized membrane regions (desmosomes)
-Cells infected with different nectins do not aggregate in layers, they aggregate randomly with each other. |
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Term
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Definition
-sites of integrin based adhesions
-actin cables that come form focal adhesions are called stress fibers
-integrins bind the ECM |
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Term
| What causes the leading edge in cell migration? |
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Definition
-Actin pushing against the cell membrane
-It occurs in a molecular ratchet |
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Term
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Definition
-makes a branched, dendritic structure of actin at the leading edge.
-The structure is called a lamellipodia and is made through the Arp2/3 complex |
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Term
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Definition
-Make protrusions called filopodia
-arp 2/3 is not involved, cdc42 instead activates formin proteins |
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Term
| Focal adhesions in cell movement |
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Definition
-RhoA drives focal adhesions which are integrin based.
-This causes thick stress fibers to link to the integrin, and for myosin tension to be placed on those stress fibers. This drives the cell forward.
-RhoA and Rac1 are usually not found in the same area. |
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Term
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Definition
-Often found in sheets of cells, epithelial
-Basal integrin adhesion, lateral cell to cell, and no apical adhesions.
-Tight junctions to make the barrier tight |
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Term
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Definition
| -Tetraspanins bind to ZO adapter proteins, linking them to the actin cytoskeleton |
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Term
| How does a cell follow a chemoattractant? |
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Definition
-In the class model it was due to G-protein activity
-The front edge was defined by PIP3 which is made by PI3K.
-PIP3 is made back into PIP2 by PTEN
-PI3K activity is all over the membrane, but 2% more on the leading edge, so more PIP3 accumulates at there.
-PTEN is active globally while PI3K is active locally
-PIP2 is converted into PIP3 by PI3K so fast at the membrane that PTEN is not accumulated there. |
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Term
| Most common division of the cell cycle |
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Definition
G1-->S (dna replicated)-->G2-->M
Go breaks off of G1 |
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Term
| What initiates events in the cell cycle? |
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Definition
cyclin dependents kinases (CDK)
-A cyclin has to bind to it
-Runs in a cycle and makes sure events happen only once and when they're supposed to. |
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Term
| How does the cell cycle machine work? |
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Definition
-The CDK-complex drives it.
-When cyclin is high enough it will produce the new cyclin and destroy the old one.
-ie cyclin Y is expressed and cyclin X is degraded |
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Term
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Definition
-are chromosomes aligned?-after M
-will conditions support cell division? after-Go/1
-Is replication complete?-After S
-Has DNA damage been repaired?-After G2 |
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Term
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Definition
-Rb must be inactivated by phosphorylation
-Ph-Rb releases E2F
-E2F makes cyclins and CDKs needed to get the cell going again |
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Term
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Definition
-When DNA damage occurs P53 is released from mdm2.
-P53 allows p21 to be transcribed and p21 keeps cdk levels down, which prevents the cell cycle from going on until dna damaga is fixed.
-If dna is damaged enough then p53 can initiate apoptotsis. |
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Term
| What initiates chromosome condensation and what is the hierarchy of chromatin? |
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Definition
-Histone phosphorylation initiates the process
- helical dna-->200-2000 fold packing-->interphase chromosomes-->10,000-20,000 fold packing-->prophase chromosomes |
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Term
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Definition
-Generated during M phase
-occurs in a semi-conservative fashion |
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Term
| How do chromosomes separate? |
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Definition
-At the start of anaphase securin is degenerated
-The degradation of securin releases separase
-Separase degrades cohesin, which holds the the sis. chromatids together |
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Term
| How chromosomes move around |
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Definition
-Kinesin organizes them on the metaphase plate
-Dynein moves them to the spindle poles during anaphase |
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Term
| How do you build a nucleus? |
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Definition
-After M-phase, nuclear envelope fragments bind to dna of chromosomes.
-The bind via the LINC complex and BAF
-The fragments fuse and form a nuclear membrane |
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Term
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Definition
-Epithelial-mesenchyme transition, happens in gastrulation
-Detach from neighboring cells and then invade tissue |
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Term
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Definition
-One cell gives rise to two completely different cells
-Result of proteins (TFs) being unevenly distributed in the parent cell
-Example in epithelium would be a separation due to apical and basal sides of the cell.
-Another example is P granules in C. Elegans development |
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Term
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Definition
-Partition mutants
-The complexes Par1/2 and Par 3/6 work in opposition of each other. ie if one is in the membrane, the other will be in the cytosol
-Before fertilization Par3/6 is on the membrane. After fertilization, membrane contraction pulls Par3/6 to one side of the cell.
-They then bind to the astral microtubules to ensure that cytokinesis results in the separations of the two proteins. |
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Term
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Definition
-When fused, the sperm dumps rhoGAP-pyk1 into the egg
-This causes rhoA to drive contraction of the cortical membrane |
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Term
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Definition
-Get rid of unwanted cells, ie to form fingers
-Get rid of damaged cells (activated by p53) |
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Term
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Definition
- Chromatin and organelles get broken down
-The membrane blebs off
-Surrounding cells phagocytose the fragments
-This avoids inflammation |
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Term
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Definition
-Epithelial cells extrude apoptotic cells
-The adjacent cells squeeze the dying cell out of the layer. |
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Term
| The extrinsic apoptotic pathway |
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Definition
-Immune cells secrete fas ligand
-fas ligand causes the fas receptor to trimerize and recruit procaspases
-the pro domain gets cleaved and the protease (caspase) gets activated |
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Term
| The intrinsic apoptotic pathway |
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Definition
-Triggered by the cell (dna damage)
-Pro-apoptotic bcl proteins are in the mitochondria and can form a channel that allows mitoch. contents to leak out
-Anti-apoptosis bcl proteins prevent bcls from forming the channel
-Cytochrome-c leaks out and complexes with apaf1 and forms an apoptosome
-Apoptosomes activate caspases |
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Term
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Definition
-Caspases can activate more caspases
-They cleave certain proteins at specific locations
-they can activate (dna protesases) or inactivate (adhesion proteins) different targets. |
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