Cell communication 1 dr WHite Flashcards

1
Q

What is signal transduction (broad) ?

A
  • cells are not isolated and must send signals to each other all the time
  • communication is between cells but signal transduction is cell to cell
  • the comunication must traverse from outside the cell to inside the cell
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2
Q

Why is signal transduction important ?

A

required for every organism

Cells, tissues, and organs need to communicate

development, coordination of metabolism

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3
Q

What is signal transduction?

A

Extracellular signaling molecules bind to specfic receptors on target cells to initiate a chain of events know as a signal transduction

2 types of responses

Fast response = change in activity or function of enzyme or proteins in the cell

Slow response = change in amount of proteins by changing in expression of genes

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4
Q

What is the process of signal transduction process?

A
  1. Ligand
  2. high affinty receptors (majority on cell surface)
  3. intracellular signal proteins
  4. effector proteins
  • Altered metabolism
  • altered gene expression
  • altered cell shape or movement
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5
Q

What are the four types of cell signaling? ***

A

endocrine

paracrine

synaptic

autocrine

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6
Q

What is endocrine singaling?

A

long distance signaling that uses freely diffusible signals that are long lasting because it takes time going through circulatory system to find a target cell

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7
Q

what is paracrine signaling?

A

acts locally by affecting cells nearby. it is not freely diffusible signal so it is short lived

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8
Q

What is synaptic signaling ?

A

this signaing acts locally and affects cells nearby and is not as freely diffusible. It is a sort lived signal and uses neurotransmitters

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9
Q

What is autocrine signaling?

A

cells respond to signals that they themselves release or release to cells of the same type or cells secrete signal to cells of the same type.

Signal causes feedbacks and binds to a receptor on its own surface

ex: growth factor

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10
Q

what is direct cell signaling?

A

immune cells or Ag-presenting cells to T cells.

Cells directly binding to each other

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11
Q

What are the types of signals sent out (as in what is the purpose they have)?

A

Survive, divide, differentiate, or DIe

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12
Q

What are the componets of the signal cascade?

A
  • Signals (ligands)
    • typically secreted by exocytosis
    • signals stay near or far
  • Receptors
    • binds specifically to signals molecules with high affinity (signals are produced in low cells)
  • Effectors
    • targets of receptors inside cells: alters activity of many different proteins and generate 2nd messengers (small diffusible molecules like cAMP and Ca2+)
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13
Q

What are the main categories of lipid signaling molecules?

A

Small lipophilic molecules : steroid hormones

Water soluble molecules - hydrophillic - growth factors

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14
Q

What in example of paracrine signaling? low testablility

A

Nitro oxide signaling (NO) - very unstable (diffuses across membrane )

Uses in circulatory system signaling

argine -> NO *

receptor and effector is an enzyme : uanidyl cyclase which produces cGMP (a secondary messenger) \

Influences muscle relaxation: blood vessels relax causing increased blood flow. and N-O can be used to prevent heart attacks

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15
Q

What different responses can acetyl choline trigger?

A

heart muscle cells -> relax

Skeletal muscle cell -> contract

salivary gland cell -> secreation of salvia

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16
Q

What are receptors?

A

they have high affinity

Cell surface :

  • External domain - binds ligand
  • Transmembrane - anchors receptor
  • Cytoplasmic domain - initates signal by change in conformation
  • Most signaling cells are hydrophilic

Intracellular : steroid receptor can have receptor in cytosol (alters gene expression in nucleus )

17
Q

What are transmembrane receptors?

A

recepetor mediated signaling

they let hyophhillic or large hormones and ligands transduce a binding event

ex: G-coupled receptors (7 transmembrane receptors)

affect olfaction, sight,, taste

CONSERVED

18
Q

What is a G coupled receptor ?

A
  • 3 parts
    • Extracellular domain which binds to ligand
    • Transmembrane domain - anchrs receptor
    • Cytoplasmic domain - assocaiaates with G protein
  • Hetrotrimeric ( alpha, beta, gamma )
  • impacts effector
19
Q

What are the componets in a G protein coupled receptor pathway?

A

Inactive receptor

Receptor G protein (trimeric G protein)

Inactive effector

20
Q

What is the G protein coupled receptor and the effector?

A

G protein coupled receptor are known by seven membrane spanning alpha helices

G proteins are guanine nucleotide binding proteins that assist in transmitting signals to intracellular targets

Effector is a downstream enzyme adenyly cyclase that generates cAMP

21
Q

What is cAMP ?

A

An important Secondary messanger that mediates cellular responese to a variety of ligands

22
Q

What is hetermotrimeric G proteins?

A

Are guanine nucleotide binding proteins that consist of three sub units desgnated alpha beta and gamma

regulate target enzymes

23
Q

What is the process of GCPR activation and what happens after?

A
  1. Inactive
  2. Activated receptor via ligand binding
  3. Activated of GPCR (G Protein Coupled Receptor) via bind to receptor
  4. G alpha is activated ; releases GDP and binds GTP and dissociates from G-beta-gamma
  5. G alpha binds and acitvated adenyl cyclase (effector enzyme)
  6. 2nd Messenger is produced (cAMP)
  7. Targets of 2nd messanger
  8. biological response

After step 5

G alpha is hydrolyses GTP to GDP, and dissociates from adenyly cyclase and binds to G-beta-gamma

24
Q

What does adenylyl cyclase do? ****

A

generates cAMP which then goes on to interact with its target proteins to cause a biological response

25
Q

What is cholera ?

A

fever, severe diarrhea, extreme dehydratio and death .

Cholera toxin modifies G protein by keeping the G-alpha int he GTP active form indefinetly.

Pumo Cl- and water out of cell inintestine and causes severe diarrhea.

In 1876, Dr. Kock Discovered the cause of Cholera: vibria Cholerae. Molecular mechanism was discovered in 1980

Dr. Snows findings represent the beginning of modern Public Health System

26
Q

What are the classes of trimeric G-proteins?

A

multiple G proteins gives diversity to different cells can respond and affect different downstream pathways

Different classes according to type G alpa

  1. G alpha s (stimulating) stimulating adenyly cyclase
  2. G alpha i (inhibiting) inhibiting adenyly cyclase
  3. G alpha O
  4. G lpha Q
  5. others
27
Q

How does cAMP work?

A
  • cAMP interacts with its target proteins cause a biological response
  • cAMP activates a protein kinase called PKA
  • A kinase will phosporylate proteins to either activate them or inactivate them
  • Inactive PKA: 2 catalytic subunits and 2 regulatory subunits -> binding of 2 cAMP molecules to regularotry subunits of tetramers results in release of active C
28
Q

What happens to the protein post phosphorylates by PKA

A

addition of 2 negative charges can change conformation of proteins

  • activation or inactivation of enzymatic target proteins
  • alteration of intracellular localization of target proteins
  • alterations in abundance of target proteins
29
Q

What does Epinephrine induces activation of PKA (protein kinease A) ?

A

Generate lots of ATP for a response to threat

Liver: glycogen breakdown to glucose

Liver: inhibition of glycogen synthesis (inactivate glycogen synthase)

Cardiac muscle - increase contraction rate

Adipose tissues: hydrolysis of tricglycerides to generate more glucose

30
Q

How does ampliation of signal transduction cascade work?

A

active PKA catalytic subunits can then phosphorylate a variety of subrates

Powerful amplification event: single hormone ligand receptor event can activate multiple adneyly cyclases

31
Q

What does it mean for a signal to be desensitized?

A

Ability to turn off or reject the signal

important: cell cycle - cancer

32
Q

What are the different types of desentizitation signal ?

A
  1. Receptor sequestration : endosome - invagination of membrane
  2. Receptor destruction: endosmes + lysomes (proteases)
  3. Hormone levels drop - decreased adenyly cyclase activity - decrease cAMP - decreased PKA activity
  4. Remove the signaling moelcule: phosphodieasterases will remove cAMP
  5. Desensitization of signal GRKs
33
Q

How does desensitization of signal GRKs?

A

proteins called GRKs: G protein Receptor Kinases

GRK phosphorylate the receptor such that another protein called arrestin will bind to the to the 3rd intracellular loop of receptor and prevents Galpha from interacting wiht the third loop of the receptor

G protein G alpha- GDP does not get converted to G alpha GTP by receptors