BIOL 300: Exam 4

signaling cascade

signaling cascade

extracellular signal molecule → receptor protein → intracellular signaling molecule → effector proteins → target cell responses

endocrine/hormonal signaling

long distance signaling

goes through the whole body through the bloodstream

paracrine signaling

local signaling

usually the signal stays within the tissue/organ

synaptic/neuronal signaling

signaling in NEURONS

the QUICKEST signaling type

contact-dependent signing

signaling that relies on cell-cell contact

can a signaling molecule have one job/effect or many?

MANY!

FAST signal response time

turning ALREADY MADE proteins on/off

SLOW signal response time

changing gene expression + creating NEW proteins

4 functions of signaling cascades

relay, amplify, integrate, distribute

relay

signal cascade function where one things turns on one other thing (think relay race)

amplify

signal cascade function where one thing turns on many others (think megaphone/speaker)

integrate

signal cascade function where a lot of info is boiled down to one decision

positive feedback

amplifies/increases activity of a pathway

negative feedback

inhibits/stops activity of a pathway

homeostasis

a biological “set-point” that the body strives to maintain (e.g. internal temperature)

why are drugs (exogenous) effective on receptors?

they’re structurally similar to proteins we already make (endogenous)

ion channel coupled receptors

exactly the same as ligand-gated ion channels

channels + receptors at the same time

GPCRs (g-protein-coupled receptors)

largest family of cell-surface receptors

where the vast majority of drugs work

go through the membrane 7 times

G protein

a lipid-linked protein

at REST, the subunits (alpha, beta, gamma) are TOGETHER

after it’s turned on, it releases GDP (low energy) and GTP binds to the activated alpha subunit (separated from the beta-gamma complex)

GDP = OFF // GTP = ON

how does the G-protein switch itself off?

the activated alpha subunit activates a target protein → GTP is hydrolyzed (now GDP) and the alpha subunit is inactivated, therefore dissociating from the target protein → inactive alpha subunit rejoins the beta-gamma complex and the g protein is off again

drug tolerance

a body getting used to a drug (like your ears after going to a concert, and you get used to the loud music so everything else seems muffled)

GPCR internalization process

a process that leads to drug tolerance/dependence

steps:

no signal: no drug given yet. GPCR is off (GDP)

signal: drug is given and binds to the receptor, which turns on (GTP)

desensitization: drug tolerance begins. beta-arrestin (think arrest=stop) attaches to the GPCR and the receptor “steps away”, still working but less than before

internalization: drug dependence begins. GPCR gets sucked into the cell (internalized) by the beta-arrestin and won’t work anymore

last stage: GPCR fully engulfed through endocytosis (engulfed in an endosome)

G_i protein

type of G protein

inhibitory (pertussis toxin)

G_s protein

type of G protein

stimulatory (cholera toxin)

what else can G proteins do?

1. turn on ion channels: e.g. G protein can turn K+ ion channel ON by binding (in active form) to the cytosol next to the channel and turns it OFF by deactivating (GTP → GDP)

2. turn on enzymes

adenylyl cyclase

enzyme that produces cAMP

signaling process

signal binds to receptor → turns on G protein (GTP) → turns on adenylyl cyclase → adenylyl creates cAMP → cAMP sends the signal to protein kinase A

which G protein (stimulatory or inhibitory) starts the production of cAMP

G_s (stimulatory), catalyzed by adenylyl cyclase

FAST cAMP pathway

GPCR → G-protein → cAMP → PKA (protein kinase) → metabolic kinase → cellular effect

proteins are already created!

SLOW cAMP pathway

GPCR → G-protein → cAMP → PKA (protein kinase) → transcription factor → cellular effect

affecting gene expression!

phospholipase C (PLC)

enzyme IN THE MEMBRANE that produces IP₃ and DAG (will be written shorthand on exam)

PLC signaling pathways

signal binds to GPCR → G-protein activates PLC → PLC produces IP₃

splits into 2 pathways:

1. IP₃ causes Ca²⁺ to be released from ER

2. IP₃ turns on DAG → activates PKC (protein kinase C)

calcium messaging pathway

PLC produces IP₃ → Ca²⁺ released → Calmodulin (does stuff by changing shape)

signaling qualities

VERY fast, sensitive, and adaptable!

RTK (receptor tyrosine kinase)

a receptor that phosphorylates tyrosine when something binds to it; AUTO phosphorylates (phosphorylates itself)

turns on RAS!

RTK pathway

RTK → RAS → MAPKKK → MAPKK → MAPK → changes protein activity (fast) or gene expression (slow)

cyclin

protein that controls/pushes the cell cycle; like checks & balances

G₀ phase

cell doing normal activity, no interest in dividing

S phase

DNA replication (begins in origins of replication / oris)

S-Cdk

starts the S-phase by binding to the right cyclin + activating the complex to activate the helicase

cohesion rings

hold together sister chromatids

M-Cdk

triggers the condensation of the chromosomes (tightens the chromatin, NO gene expression)

MAPK

FAST cascade that has positive feedback, influences Cdc25 activity

condensin rings

loop around loose chromosome and turns it into an X-shape

cell cycle steps

interphase (G₁, S, G₂) → prophase → prometaphase → metaphase → mitosis → anaphase → telophase → cytokinesis

prophase

1st cell cycle phase with TWO centrosomes, and the chromosomes are condensing

prometaphase

2nd cell cycle phase where the nuclear envelope is being broken down

metaphase

3rd cell cycle phase where the microtubules pull chromosomes to the middle

anaphase

4th cell cycle phase where X-shaped chromosomes are split in half, and cohesion rings break

telophase

5th cell cycle phase where the nuclei are recreated

cytokinesis

final cell cycle phase where the cytoplasm is divided in two by a contractile ring of actin and myosin filaments

centrosome

major microtubule organizing center

centrosome cycle

centrosome duplicated → move to opposite poles during mitosis → each attach to their own microtubules/mitotic spindles

aster microtubules

type of microtubule that comes out from the centrosome and attaches to the rest of the cell to stabilize it

kinetochore microtubules

type of microtubule that binds directly to DNA

interpolar microtubules

type of microtubule that connects to each other between poles

APC

anaphase promoting complex; signaling molecule

active separase

enzyme that separates cohesion rings

cohesion complex

holds chromosomes together in metaphase

chromosome separation triggered by APC

inhibitory protein (securin) and separase form a complex → (2 pathways)

• active APC leads to ubiquitylation + degradation of securin

• cohesion rings are cleaved and dissociated by active separase during anaphase

breakdown and reformation of nuclear membrane

interphase nucleus → phosphorylation of nuclear pore proteins and lamins → prometaphase (break down nuclear membrane through phosphorylation) → dephosphorylation of nuclear pore proteins and lamins → telophase (makes 2 new nuclei) → continued fusion of nuclear envelope vesicles → cycle restarts

cytokinesis in plant cells involves what?

formation of a cell wall

apoptosis

programmed cell death; very important, highly controlled, important for structural development, quick, and “environmentally friendly” (doesn’t harm nearby cells)

what is an example of organ size control?

through the process of apoptosis, the balance between cell birth and cell death is kept. an example of this is in the liver: exposing the human liver to phenobarbital (a drug that stimulates liver cell division) will make the liver enlarge

necrosis

MESSY, causes inflammation and damage to neighbors (like a sudden death)

caspases

family of proteases (break down proteins) important in apoptosis

amplifying caspase cascade

cascade that regulates apoptosis; IRREVERSIBLE and tightly controlled

one molecule of active initiator caspase → activates multiple caspases → turns on more → leads to cleavage of nuclear lamin and THEN the cleavage of cytosolic protein

Bcl-2 proteins

family of proteins that regulate apoptosis (there are anti and pro apoptotic ones)

anti-apoptotic Bcl-2 proteins

Bcl-2, Bcl-XL

pro-apoptotic Bcl-2 proteins

Bax, Bak, Bad

mitrochondria’s role in caspase cascade

cause caspase cascade to start by releasing cytochrome C

3 classes of signals to the cell from the environment

(pro) survival factors: suppress apoptosis

mitogens: stimulate cell division

growth factors: stimulate cell growth

note: these signals are NOT mutually exclusive, so a combination of them can be sent at once!

how do survival factors limit the number of neurons we’re born with?

we grow a TON of neurons before birth, but there’s not enough survival factors so the ones without them go through apoptosis

growth factors stimulating cell growth

increased protein synthesis + decreased protein degradation = cell growth!

myostatin cow example

myostatin: inhibitory growth factor that tells our muscles when to stop growing; if there is a mutation in myostatin genes, there is a lot of uncontrolled muscle growth… sometimes cows are bred for muscle mass, where this mutation occurs

cellulose

a big part of the plant wall, and the reason why plant cells don’t need a matrix

4 major types of animal tissue

connective (needs a LOT of extracellular matrix b/c it has more mechanical stress), epithelial, nervous, muscular

collagen

building material in the ECM

what is leather made of?

pickled collagen

how do collagen molecules organize?

they form triple-stranded collagen molecules (BIG, THICK SPIRAL!)

fibroblasts

make and maintain/break down the ECM

Ehlers-Danlos syndrome (EDS)

group of diseases due to collagen not forming correctly (rly stretchy skin example)

where does the strength come from for the plasma membrane?

cytoskeleton, integrin, and ECM (not strong on its own)

integrins

binds + creates a signal

decel/recel technology

removing all cells from an organ and leaving only the ECM, then the organ is injected with the patient’s cells. the cells recognize the ECM and function properly

GAGs

form bottle brush like structures (hydrophilic) and take up a lot of room

hyaluronan molecule (hyaluronic acid): commonly used in skin care

chondroitin sulfate: commonly used in joint care

epithelia

a layer in the cell that keeps some molecules in and others out, takes up nutrients and exports waste, and contains receptors for environmental signals; apical and basal sides have DIFFERENT FUNCTIONS!

e.g. epithelium of the gut lines the cell

apical

side of epithelia cell that faces the air or watery fluid (“top”)

basal

side of epithelia cell that is deeper into the organ (“bottom”)

tight junction

seals neighboring cells together in an epithelial sheet to prevent leakage of molecules between them

adherens junction

form a strong, continuous “belt” around the epithelium

desmosome

type of cell-cell junction that joins the intermediate filaments (STRONG) in one cell to those in a neighboring cell

gap junctions

connexons connect cells via the cytoplasm

can OPEN and CLOSE!

hemidesmosome

“half” desmosomes that connect intermediate filaments to the basal lamina

how is the organization of tissue preserved?

cell communication, selective cell-cell adhesion, and cell “memory”

stem cells

cells that can differentiate into many types of cells

divide a LOT (dividing precursor cells do the most of that)

mature into terminally differentiated cells

where in the lumen of the gut are stem cells located?

at the BOTTOM of the crypt

hemopoietic (blood) stem cell

stem cell in the blood (an organ); can make ALL the cell types in that organ

Wnt pathways in the gut

INACTIVE in villi (if active here, it’d cause cancer)

ACTIVE in crypt

without Wnt signal: APC ON, beta-catenin OFF

with Wnt signal: Wnt → signal cascade → beta-catenin → cell division (APC OFF, beta-catenin ON)

induced pluripotent cells

have the potential to become many things; created by taking any cell and forcing it to become a stem cell