Cell 360 Exam 3 (final exam)

Autocrine

a cell signals to itself

Juxtacrine

adjacent cells signal to each other, cells are touching

Endocrine

blanket term for signaling throughout an organism, from the whole body

Paracrine

signaling over a distance

FRET

- florescence resonance energy transfer

- tests whether one protein is activating another *protein interactions*

- transfer is sensitive to distance, two molecules have to get close together

PAABD experiment

binds specifically to phosphorylated amino acids--works THROUGH FRET to test if one thing is coming close to another and causing it to fluoresce

- phosphorylated amino acid binding domain

Short/simple

- short response, little amplification, more ligands cause more response, GRADUAL response (only some cells, then more and more cells)

Long/complex

- binary response (b response)

- a LOT of amplification

- requires more activation to get a response

- reach a threshold THEN the response occurs

Positive feedback

signal stays even when there is no ligand present, the signal is propagated by the system

Negative feedback

shuts off the system, removes the phosphate groups so the system turns off

Pinocytosis

Caveolin coat, Sphingolipids/Cholesterol, Dynamin

"cell drinking"--membrane is budded off to maintain the same tightness/pressure

- constantly occurring

Caveolin

Coat for pinocytosis

Phagocytosis

Uses PIP3 lipid

"eating" big things, large solid particles

PTEN

converts PIP3--> PIP2

phosphotase, removes phosphate group

PI3K

converts PIP2--> PIP3

- kinase (adds phosphate group)

AP2

Facilitates clatherin coating by binding to PIP2

ESCRT

Helps sort membrane protiens into MVBs to go to lysosome for degradation

Glycocalyx

a thick carbohydrate layer that protects proteins and lipids from degradation

- on the inside of the endosome

Filopodia

long, thing projects of bundled actin, spine-like

*bundled actin*

*the most forefront structure on the leading edge of the cell*

Cdc42

GTPase that interacts with WASP to activate Arp2/3 for filopodia formation *front of the cell*

Limellopodia

broad extensions containing branched actin

- filopodia poke out from here

- polymerication stimulated by Tac1

Rac 1

GTPase that activates Arp 2/3 for lamellipodia formation

Stress fiber

complexes of actin and myosin that extend between two focal adhesions and located mainly in the rear part of the cell

Rho A

GTPase found at the back of the cell

Rho kinase--> Myosin light chain kinase--> myosin light chain--> contraction of stress fibers

- helps the cell to de-adhere and contract

FAK

activated by RhoA to cause focal adhesions to fall apart

*only active at the back of the cell*

- integrins are endocytosed and recycled to a forming focal adhesion

Prophase

DNA condenses and spindle poles separate to opposite sides of the nucleus *centrosome duplicates*

Condensin

multiprotein complex that helps package DNA into higher order structures to untangle it--activated by phosphorylation by m-CDK

Cohesion

- holds sister chromatids together after replications

- friendship bracelet of the cell

- specific to mitosis

Prometaphase

nuclear envelope breaks down and microtubules find the chromosomes

- Nuclear envelop disassembly--> lamins get phosphorylated which cause them to get MORE FLEXIBLE and break down

NDC80

links the + end of the microtubule to the kinetochore of each chromosome to ensure that division occurs

Kinetochore

binds to NDC80 and thus the MTs when the chromatids are getting pulled apart

Metaphase

chromosomes line up at the metaphase plate and are connected to spindle poles on either side

Anaphase

sister chromosomes separate and move towards two spindle poles

--Depoly at the + end

--Depoly at the - end

--Depoly of astral MTs

*depoly pulls the chromosomes towards the poles of the cell*

Securin

sequesters separase--degraded when anaphase is initiated

Separase

inactivates cohesion so the two chromosomes will come apart

Telophase

chromosomes arrive at the spindle poles and chromosomes begin to decondense *nucleus reformed*

- start to make the contractile ring of cytokinesis

- nuclear envelope fragments bind to BAF on separated chr and fuse to make a new nuclear envelope

BAF

Helps reassemble nuclear envelope during telophase

Cytokinesis

cells separated by the contractile ring--contractile ring is made of myosins and actins (a stress fiber)

- division occurs at the spindle midzone

Rho A

Activates stress fibers

Contractile ring

- actin/myosin filaments are arranged at the midzone for this scructure

-is activated by Rho A

Rb

For G0 to G1

checkpoint binds transcription factor E2F, becomes phosphorylated by CDKs to release E2F

E2F

G1 to S phase

transcription factor that turns on genes for cyclins and CDKs

Aurora B

TRANSITION, checks if DNA replication is finished, activates PlK1 when done

PlK1

TRANSITION inactivates Wee1 (checkpoint) and activates cdc25 (transition)

P27

checkpoint Stops CDK-cyclin complex by binding

P53

checkpoint activates P27 and is phosphorylated by ATM/ATR

ATM/ATR

checkpoint checks for DNA damage, phosphorylates P53 (checkpoint) to activate it, inactivates cdc25 (transition)

APC

TRANSITION E3 that combines with cdc25 (transition) to ubiquitinate m-cyclins and securin for destruction--> allows anaphase to move forward

Cdc25

TRANSITION dephosphorylates CDKs to activate (phosphotase)

Wee1

checkpoint, phosphorylates m CDKs to inactivate them (kinase)

Sac complex

checkpoint checks if microtubules are attatched to chromatids, inhibits cdc20 until microtubules are attached

- binds and sequesters cdc20 (transition) so APC can't activate

Cdc20

transition activates the APC complex

Tumor supressor genes

genes that normally stop/arrest the cell cycle

- LOSS of function mutation associated with cancer

Oncogenes

genes the normally promote (activate) the cell cycle

- GAIN of function mutations associated with cancer

Apoptosis

cells break down into chromatin and organelles, fragment into pieces, then pieces (blebbing) are consumed through phagocytosis

- controlled process less dangerous for the cell because all the components are carefully broken down

- cellular components maintained in apoptotic bodies

- very common and can happen rapidly

Necrosis

response to acute injury and leads to inflammation

- cell is ruptured and the cellular components are spilled out

- much more dangerous if a virus is involved because then the virus would explode all over the cell

Caspase

cytosine in the active site and aspartic acid where they cleave proteins

- pro-caspase= initial, inactive form

Initiator caspase

activated by apoptotic signals and CLEAVE executioner caspases to activate them

- come together in large complexes to form dimers

- each initiator caspase cleaves it's partner

Executioner caspase

cleaves other substrates, produce the actual effects underlying apoptosis

1. Adhesion proteins--> Anoikis (extrusion of dead cells)

2. DNA nucleases--> iCAD, going to cut down DNA

3. Actin regulators--bleb

4. Flippase--"eat me" signal

5. Lamins--nuclear breakdown

Hallmarks of cancer

1. Cell growth and division without the proper signals to do so→ broken transitions, gain of function oncogenes

2. Continuous growth and division even when there are signals to stop→ broken checkpoints, loss of function tumor suppressor genes

3. Avoidance of programmed cell death

4. Limitless number of cell divisions (not necessarily faster)

5. Promoting blood vessel construction

6. Invasion of tissue and formation of metastases

Carcinoma

epithelial cells contains most common cancers in the aged, breast, prostate, lung, pancreas, colon

Sarcoma

connective tissue bone, cartilage, fat, nerves, develops from cells originating in mesenchymal cells outside the bone marrow

Lymphoma and leukemia

hematopoietic (blood forming) cells leave the marrow and mature in the lymph nodes and blood

Germ cell tumor

pluripotent cells presenting in the testicle or ovary

Blastoma

precursor cells or embryonic tissues more common in children, contains different types of cells like teeth and hair

Gain of function

requires ONE mutation event which activates an oncogene

- dominant mutation, increased activity

- usually not inherited

- more rare

Loss of function

requires MANY mutation events which inactivates a tumor supressor gene

- more common

- recessive

- inherited

- the working chromosome can be mutated or broken through homologous recombination to cause cancer

Astral microtubules

on the opposite sides of daughter cells--anchor to the cell wall, sets up the front side of the daughter cell that's being created

*shortens from the + end to pull the centrosomes farther apart*

Kinetochore microtubules

attach to the kinetochore, help the splitting between the chromatids

*shorten from BOTH the + and - ends*

Interpolar microtubule

overlaps between the two daughter cells, pushes against each other so the centrioles go in opposite directions

*recruits RhoA for cytokinesis*

Par 1

prevents par 3/6 binding, pushes the par 3/6 towards the apical (top) of the cell

Par 3/6

binds to tight junctions, recruits crumbs

Scribble

binds to same side (theoretically) as par 1 and prevents crumbs binding

Frizzled/Disheveled

binds to Van Gogh on a neighboring cell

Van Gogh

recruits prickle

Prickle

keeps frizzled/disheveled away

CDK

push the cell cycle forward--activated by cyclins to initiate the next transition

- inactive until bound by a cyclin

- levels of cyclin change, but CDKs do not change

Cyclin

transition proteins that cycle in their expression, push the cell forward in the cell cycle

- determines the target of the kinase, one kinase can have many targets

Intrinsic pathway

This pathway is initiated by internal cellular stress or damage, such as DNA damage

Activation of pro-apoptotic Bcl proteins

Formation of channels in the mitochondrial membrane, leading to the release of cytochrome C i

Formation of the apoptosome

Recruitment and activation of initiator caspases

Activation of executioner caspases

Cleavage of target proteins

extrinsic pathway

This pathway is triggered by external signals that bind to death receptors on the cell surface

Binding of a ligand to a death receptor

Recruitment of adaptor proteins (e.g., FADD) to the death receptor, forming the Death-Inducing Signaling Complex (DISC)

Recruitment and activation of initiator caspases

Activation of executioner caspases \

Cleavage of target proteins by executioner caspases

Hydrophobic second messengers

Diacylglycerol, phosphatidylinositols

Hydrophilic second messengers

cAMP,cGMP, IP3, Ca2+

Gas second messengers

NO, H2S, CO