lec 20

Question 1

signal transduction path

Answer 1

mechanism for passing info into the cell
- cascade of biochem rxns that leads to a specific response

Question 2

overview of signal transduction path

Answer 2

starts w/ ligand binding to recept
ends w/ target mech. (response)

Question 3

what are the responses in the signal transduction path?

Answer 3

1. migration
2. growth
3. proliferation
4. survival
5. apoptosis
6. differentiation
7. adhesion

Question 4

target mech.

Answer 4

cells = dependent on many extracellular signaling molecules that act in combination to elicit a specific response
- transcriptional activation/inhibition of genes
- rates of enzymes
- endocytosis, exocytosis
- cell movement

Question 5

signal transduction cascade

Answer 5

complexity = control

Question 6

why have complexity in signal transduction cascade?

Answer 6

1. regulation
2. coordination and integration of many signals
   - convergent and divergent cross-talks

Question 7

feedback loops

Answer 7

positive: product stimulates own production/activation
negative: product inhibits earlier step in same path

Question 8

cross-talk

Answer 8

When 1 or more components of the signal transduction path affect another path

Question 9

convergent cross-talk

Answer 9

signals from different ligands signaling through unrelated recept. converge on a common intracellular signaling protein/effector after binding to a specific ligand
- Paths converge to elicit the same response

Question 10

divergent cross-talk

Answer 10

signals from the same ligand diverge to activate various different intracellular signaling proteins/effectors to elicit different responses

Question 11

types of intracellular signaling

Answer 11

1. contact-dependent (“juxtacrine signaling”
   - cell and ECM to cell
   - communicating/gap junction
2. paracrine
3. synaptic
4. endocrine

Question 12

juxtacrine signaling

Answer 12

signal to neighboring cells
- membrane-bound ligands
> if cell to cell signaling
- ECM
> if ECM to cell signaling
- small cytoplasmic molecules
> if gap junctions

Question 13

paracrine signaling

Answer 13

local diffusion, further than neighboring cells but generally to target cells w/n tissue
- growth factors: proteins that stimulate growth
> proliferation and differentiation
- cytokines
- gases
when secreted molecule acts on the same cell that makes it = autocrine

Question 14

synaptic signaling

Answer 14

short distance diffusion, systematic action, signal specifically between cells w/n a synapse
- neurotransmitter
> released by neurons, received by neurons, ,muscle or glands

Question 15

endocrine signaling

Answer 15

systemic, long-distance diffusion in the circulatory system
- hormones = released into the bloodstream

Question 16

what are the common characteristics of endocrine and synaptic signaling?

Answer 16

1. Large, complex multicellular organisms need systematic
2. signaling to coordinate
3. func at distant parts of the body

Question 17

synaptic signaling vs. endocrine

Answer 17

both act on long range
- synaptic is faster
> adaptation for systemic regulation in Animalia
> fast electrical control of signal release

Question 18

what are the 2 kinds of peripheral Nervous System (NS) neurotransmitters?

Answer 18

Somatic and Automatic NS

Question 19

Somatic NS

Answer 19

Voluntary movement of skeletal muscle
- motor neurons: acetylcholine (ACh)

Question 20

Automatic NS

Answer 20

involuntary movement of the internal organs
1. sympathetic (internal homeostasis, “flight or fight” response) : norepinephrine (NE)
2. parasympathetic (“ rest and digest” response): ACh

Question 21

endorphins (endogenous morphine)

Answer 21

1. neurotransmitter
2. made by various cells w/n CNS in response to different triggers
3. signal to regions of brain that respond to pain and deal w/ emotions
   - inhibit transmission of pain
   - affect feelings of pleasure
4. bind opioid recept. expressed on responding cells
5. implicated in placebo effect
6. misregulated endorphin signaling = implicated in OCD, anxiety and depression
7. opiate addiction

Question 22

recpt desensitization

Answer 22

uncoupling of recept from signaling cascade
- occurs after prolonged exposure to ligand
1. inactivation
- recept = altered that it disconnects from its cascade
2. sequestration
- recept = temporarily internalized
3. down regulation
- destroyed in lysosome after internalization

Question 23

ghrelin

Answer 23

hormone made mainly by endocrine cells in the stomach
- travels through the circulatory system to hypothalamus in brain
- hunger

Question 24

leptin

Answer 24

hormone made by adipose cells
- travels through the circulatory system to the hypothalamus in the brain
- fullness
- increased by insulin, in the middle of the night, and perceived stress
- decreased by sleep deprivation

Question 25

how do ghrelin and leptin communicate?

Answer 25

They work in apposition to one another in the regulation of body weight homeostasis - act on a common pop. of neurons

Question 26

oxytocin

Answer 26

hormone released (prominently) by cells in the hypothalamus - signals to cells in various regions of the CNS facilitates pair bonding, birth, maternal bonding, lactation, decreased stress and anxiety in socially-dependent matter implicated in neuropsychiatric disorders

Question 27

recept

Answer 27

whether a hormone, neurotransmitter growth factor, cytokine or juxtacrine signaling molecule - start communication to cell by binding receptors 1. transmembrane receptors proteins (cell surface) 2. Intracellular receptors

Question 28

G protein-coupled recept. (GPCR)

Answer 28

1. recept that interact w/ trimeric G proteins on the intracellular side 2. all have 7 transmembrane domains 3. associated w/ different downstream paths - all act through the trimeric G proteins 4. func: regulating the activity of the Trimeric G protein - proteins activated via GTP binding once activated - trimeric G proteins activate separate PM protein (target) > mediates interaction between GPCR and target

Question 29

GTP hydrolysis to GDP is a type of a "molecular switch" Activation process

Answer 29

Activation: GTP binding protein = induced to exchange its bound GDP for GTP - GEFs (guanine nucleotide exchange factor) increase G protein exchange of GDP for GTP - GPCR acts as GEFs when they activate trimeric G protein

Question 30

GTP hydrolysis to GDP is a type of a "molecular switch" Inactivation process

Answer 30

Inactivation: G proteins hydrolyze bound GTP to GDP - G proteins have intrinsic GTPase activity (to hydrolyze GTP to GDP) - GAPs (GTPase Activating Proteins) speed up GTPase activity and affect the conformation of G proteins, which hydrolyze GTP more efficiently

Question 31

trimeric G protein structure and function

Answer 31

1. subunits: alpha, beta and gamma 2. often bound to recept in inactive form - when inactive = alpha = GDP bound 3. in and activation regulate downstream activity a. G protein Activation i. ligand binds to GPCR ii. GPCR acts like GEFs which causes alpha to release GDP and that allows GTP to bind iii. resulting conformation change allows active alpha and beta-gamma to interact w/ targets b. G protein inactivation - G proteins have GTPase activity which occurs when GTP on alpha is hydrolyzed to GDP

Question 32

classic G proteins paths

Answer 32

1. cyclic AMP path 2. phospholipase C (PLC) path