Cell communication 1 dr WHite Flashcards
What is signal transduction (broad) ?
- 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
Why is signal transduction important ?
required for every organism
Cells, tissues, and organs need to communicate
development, coordination of metabolism
What is signal transduction?
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
What is the process of signal transduction process?
- Ligand
- high affinty receptors (majority on cell surface)
- intracellular signal proteins
- effector proteins
- Altered metabolism
- altered gene expression
- altered cell shape or movement
What are the four types of cell signaling? ***
endocrine
paracrine
synaptic
autocrine
What is endocrine singaling?
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
what is paracrine signaling?
acts locally by affecting cells nearby. it is not freely diffusible signal so it is short lived
What is synaptic signaling ?
this signaing acts locally and affects cells nearby and is not as freely diffusible. It is a sort lived signal and uses neurotransmitters
What is autocrine signaling?
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
what is direct cell signaling?
immune cells or Ag-presenting cells to T cells.
Cells directly binding to each other
What are the types of signals sent out (as in what is the purpose they have)?
Survive, divide, differentiate, or DIe
What are the componets of the signal cascade?
- 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+)
What are the main categories of lipid signaling molecules?
Small lipophilic molecules : steroid hormones
Water soluble molecules - hydrophillic - growth factors
What in example of paracrine signaling? low testablility
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
What different responses can acetyl choline trigger?
heart muscle cells -> relax
Skeletal muscle cell -> contract
salivary gland cell -> secreation of salvia
What are receptors?
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 )
What are transmembrane receptors?
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
What is a G coupled receptor ?
- 3 parts
- Extracellular domain which binds to ligand
- Transmembrane domain - anchrs receptor
- Cytoplasmic domain - assocaiaates with G protein
- Hetrotrimeric ( alpha, beta, gamma )
- impacts effector
What are the componets in a G protein coupled receptor pathway?
Inactive receptor
Receptor G protein (trimeric G protein)
Inactive effector
What is the G protein coupled receptor and the effector?
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
What is cAMP ?
An important Secondary messanger that mediates cellular responese to a variety of ligands
What is hetermotrimeric G proteins?
Are guanine nucleotide binding proteins that consist of three sub units desgnated alpha beta and gamma
regulate target enzymes
What is the process of GCPR activation and what happens after?
- Inactive
- Activated receptor via ligand binding
- Activated of GPCR (G Protein Coupled Receptor) via bind to receptor
- G alpha is activated ; releases GDP and binds GTP and dissociates from G-beta-gamma
- G alpha binds and acitvated adenyl cyclase (effector enzyme)
- 2nd Messenger is produced (cAMP)
- Targets of 2nd messanger
- biological response
After step 5
G alpha is hydrolyses GTP to GDP, and dissociates from adenyly cyclase and binds to G-beta-gamma
What does adenylyl cyclase do? ****
generates cAMP which then goes on to interact with its target proteins to cause a biological response
What is cholera ?
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
What are the classes of trimeric G-proteins?
multiple G proteins gives diversity to different cells can respond and affect different downstream pathways
Different classes according to type G alpa
- G alpha s (stimulating) stimulating adenyly cyclase
- G alpha i (inhibiting) inhibiting adenyly cyclase
- G alpha O
- G lpha Q
- others
How does cAMP work?
- 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
What happens to the protein post phosphorylates by PKA
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
What does Epinephrine induces activation of PKA (protein kinease 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
How does ampliation of signal transduction cascade work?
active PKA catalytic subunits can then phosphorylate a variety of subrates
Powerful amplification event: single hormone ligand receptor event can activate multiple adneyly cyclases
What does it mean for a signal to be desensitized?
Ability to turn off or reject the signal
important: cell cycle - cancer
What are the different types of desentizitation signal ?
- Receptor sequestration : endosome - invagination of membrane
- Receptor destruction: endosmes + lysomes (proteases)
- Hormone levels drop - decreased adenyly cyclase activity - decrease cAMP - decreased PKA activity
- Remove the signaling moelcule: phosphodieasterases will remove cAMP
- Desensitization of signal GRKs
How does desensitization of signal GRKs?
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
