Cell to Cell communication Flashcards
connexon
part of electrical synapse-gap junctions
-makes up gap junction, connects cells
connexin
make up connexon, 6 molecules
-ions pass through the gap junction, therefore it conducts electric current from cell to cell
target cell
any cell that has the specific receptors for the secreting cell chemical message and is in range of message
-receptors can be in membrane or inside cell
4 types of chemical message systems
- direct contact
- neurocrine
- endocrine
- paracrine
direct contact
one cell displays message (secreting cell) on cell membrane, other cell is in direct contact and receptors contact message
neuroncrine
chemical synapse between cells, releases neurotransmitter.
-extremely localized
paracrine
message released locally into surrounding tissue fluid
-target cells are any cell within area that have receptor
endocrine
secreting cell releases message into bloodstream
- target cells are any cells that possess receptors for message
- chemical message=hormone
intrinsic control
secreting cell releases message because of its assessment of local conditions or intracellular conditions
extrinsic control
secreting cell releases the message in response to signals from other cells
examples of peptide transmitters
pituitary hormones, growth factors, neuropeptides
examples of water soluble transmitters
neurotransmitters, histamine, epinephrine
examples of lipid soluble transmitters
steroid hormones, prostaglandins, thyroxin, vitamin D
examples of gaseous transmitters
NO, carbon monoxide
location of receptor for steroids and thyroxin
inside cell, nucleus actually. Bind to DNA binding protein. influences transcription of certain genes
2 types of cell surface receptors for water soluble transmitters
- chemically gated channel, receptor is channel
2. receptor is trigger for intracellular second messenger system
5 types of chemically gated channels
- sodium
- potassium
- calcium
- chloride
- cation
5 types of secondary messenger systems
- caclium
- cyclic AMP
- cyclic GMP
- Phosphatidyl inositol
- tyrosine kinase
3 things that second messenger pathways must accomplish
- get message inside cell to alter function of intracellular enzymes
- amplifying signal so large numbers of intracellular enzymes are affected by small numbers of first messenger (cascade amplification)
- producing a coordinated response, so some intracellular enzymes are activated while the opposing enzymes are inactivated
calcium as a second messenger
- important factor in regulation of cellular activity
- enter cell from plasma membrane or released intracellularly
concentrations of ca within cell
lower concentration within cell that tissue fluid, Ca atpase is constantly pumping Ca out of cell
what does ca entering cell do
depolarization of membrane and acts like a second messenger
what does ca bind to within the cell
calmodulin (cytoplasmic protein)
-4 binding sites that exhibit cooperative binding
what shape graph does calmodulin give
sigmoid curve, so low to sudden increase high and plateaus off (s like)
what type of modulator is ca/calmodulin binding complex
allosteric modulator for enzymes
important type of stimulated enzyme by ca/CAM?
ca/CAM dependent protein kinase enzyme
-protein kinase will phosphorylate other enzymes to activate or inactivate them
what is a kinase
enzyme that catalyzes the transfer of phosphate groups from high energy molecules to substrates
what happens when you increase the number of calmodulins inside cell
increase binding of ca, increase response. increase number of full ca/CAM protein kinase, more reaction of phosphorylated proteins
what is the GTP binding protein (G-protein)
secondary messenger system
- 3 subunits, alpha has a GDP bound to it when inactive.
- cell receptor acts as a allosteric modulator, G-protein releases GDP when transmitter binds
- higher affinity for GTP when activated
how long does an activated alpha protein last
as long as it is bound to GTP molecule
what does the activated G-protein do
-acts as an allosteric modulator to some other protein in cell
what deactivates the g-protein
- automatically deactivates itself
- automatic shutoff switch or timer
- alpha unit has intrinsic GTPase activity
what does the intrinsic gtpase activity do for an alpha protein
it can hydrolyze the GTP to form GDP and P. now has GDP bound and is no longer active.
-reassociates itself with B and Gamma subunits and the receptor
The cAMP secondary messenger system
ATP->(adenylate cyclase) cAMP->(cAMP phosphodiesterase)AMP
- secondary messenger is cAMP in cell
- in order to control it, we must control enzyme that makes it and enzyme that destroys it
what makes cAMP from ATp
adenylate cyclase (AC)
what breaks cAMP down to AMP
cAMP phosphodiesterase
how to increase cAMP
stimulate AC or inhibit phosphodiesterase
how to decrease cAMP
inhibit AC or increase phosphodiesterase
what controls Adenylate Cyclase
- stimulated by stimulatory G-protein (Gs)
- inhibited by inhibitory G-protein (Gi)
what do we assume about cAMP phosphodiesterase
always active, so AC affects activity of cAMP
what type of receptors are always linked to Gs proteins
beta-adrenergic receptors
Ex. of cAMP loop (epinephrine)
- epinephrine binds to its receptor on surface of muscle cell
- Gs protein activates adenylate cyclase
- activation of Gs causes cytoplasmic cAMP to increase
- cAMP acts as an allosteric modulator, stimulating a cAMP dependent protein kinase: protein kinase A (PKA)
- pka phosphorylates different types of enzymes
- epinephrine no longer bound, everything stops
How long does the allosteric effect of the Gs protein last
not long because of the GTPase activity of Gs
Composition of PKA
four subunits, two regulatory subunits and 2 catalytic subunits
- cAMP binds to the regulatory subunits (4 slots) and activates the catalytic subunits
- catalytic subunits break off and perform actual phosphorylation
what happens if cAMP levels fall
regulatory subunits release cAMP and bind back to the catalytic subunits, stopping their activity
different enzymes that pka stimulates in the epinephrine example
- glycogen phosphorylase kinase
- glycogen synthase
glycogen phosphorylase kinase
stimulates glycogen phosphorylase to break down glycogen to glucose
glycogen synthase
inhibited by being phosphorylated
net effect of these two enzymes
glycogen breakdown is stimulated while glycogen synthesis is inhibited. results in increase glucose in muscle cell
what happens when epinephrine is no longer bound
- Gs inactivates itself and remains inactive
- adenylate cyclase is no longer stimulated by Gs
- cAMP phosphodiesterase breaks down the cAMP, decreasing concentration
- PKA is no longer active because of low cAMP
- Glycogen synthase and glycogen phosphorylase are dephosphorylated by protein phosphatase
- glycogen synthesis is stimulated and glycogen breakdown is inhibited, lowering glucose and slowing glycolysis
Phosphatidyl Inositol second messenger system
PIP2 is a phosphoglyceride that can be cleaved into two different second messengers
-activation of the receptor for primary message causes activation of the Gp protein, which is positive allosteric modulator for phospholipase C
Phospholipase C
enzyme that splits a phosphoglycerid in two, it splits PIP2 into diacylglycerol (DAG) and inositol triphosphate (IP3)
Diacylglycerol (DAG)
glycerol and two fatty acids.
-hydrophobic molecule and it stays in the membrane bilayer. acts as a second messenger and a positive allosteric modulator of PKC which causes phophorylation of enzymes
Inositol triphosphate (IP3)
phosphate containing the hydrophilic part. molecule released into cytoplasm. acts as second messenger by opening and chemically gated Ca++ channel in endoplasmic reticulum, causing cytoplasmic Ca++ to increase
ca++->CAM->ca+=/CAM kinase-> phosphorylation of enzymes
examples of receptors that are enzymes activated by the first message
- receptor is allosteric enzyme with the first message as a positive allosteric modulator
- tyrosine kinase
- guanylate cyclase
tyrosin kinase
receptor/enzyme for peptide growth factors and insulin
-binding activates the enzyme and causes phosphorylation of other proteins in the cell
guanylate cyclase
receptors for the gaseous transmitter nitic oxide, and also some peptide hormone receptors catalyze the formation of cGMP which is analogous to cAMP
