LECTURE 4 Flashcards
mechanisms of intercellular communication
- Gap junctions
- Autocrine secretion
- paracrine communication (mediator)
- contact dependent communication
- synaptic communication
- endocrine communication
- *require close vicinity
- *few microns
Autocrine secretion
secreting mediator affects cell
mediator released= autocrine mediator
Gap junctions
- Gap junctions
- connexin proteins
e. g heart muscles become excited - autocrine secretion
paracrine communication
first cell has effect
contact dependent communication
cell to cell communication
effect on surface and receptor
synaptic communication
neuron has exon (short or long), when stimulated- AP to terminal which releases mediators which act on adjacent side
mediator: neurontransmitter
* *distance can be long, depending on length of axon
* *controls muscle movement
endocrine communication
first cell releases mediator into blood stream
can go to other parts of body
has a target cell with receptor that recognises the receptor
mediator: hormone
receptors:
are bifunctional molecules that recognise ligands (molecule that can bind to receptor);
approximately 10^-9 molar concentration
can do two things:
- recognise mediator
- in target cell evoke biological response
- high affinity for mediator
- molecule recognised by receptor: ligand
- ligand +receptor= reversible
- saturated ( if every receptor has one binding site, all ligands bound to receptor = 100%)
- specific
- biological response
1-5 regarding binding
6 biological response*
** see lecture notes from Dr. Hunyady
..etc
classes of membrane receptors
TYPE I = ion channel:
ECF ligand: GABA Ach ATP
membrane currents: Cl- Na+. K+ Ca 2++
ICF ligand: cAMP, cGMP. insP3, Ca++ (Na+, k+, Ca++)
TYPE 2: G protein coupled
neurotransmitters, pepties, odorants, cytokines and lipids (beta gamme subunits activate channels, alpha activates enzymes..
**cyclases generate cAMP, cGMP, phospholipase that generate IP3 and diacylglycerol
** phospholipases generate arachidonic acid and its metabolites
TYPE 3= catalytic
ANP, insulin and EGF (receptor guanylyl cyclase, receptor tyrosine kinase
TYPE 4= nuclear receptors:
1. steroid hormones (mineral corticoids, glucocorticoids, androgens, estrogens and progestins
(bind to regulatory sequences in DNA and increase or decrease transcritpion
- miscellaneous hormones= thyroid, vit D, retinoic acid, prostaglandins
(bind to reg sequences in DNA and increase or decrease gene transcription
4 types of PM receptors**
ion channel linked receptors
ligand gated ion channels
mediate direct and rapid synaptic signalling b/w electrically excitable cells
*neurontransmitter bind to receptor and either open or close the ion channel
=>changing ionic permeability of the ion channel
4 types of PM receptors**
GPCRs
GPCRs (g protein coupled receptors)
regulate activity of other proteins i.e enzymes and other channels
mediator: heterotrimeric G proteins (α, β, γ)
* *activate or inhibit downstream target proteins that regulate signalling pathways
Catalytic receptors
4 types of PM receptors**
4 types of PM receptors**** ion channels GPCRs Catalytic receptors transmembrane receptors
function as enzymes
RIP (regualted intramembrane proteolysis)
cytosolic peptide fragment that enters the nucleus and regulates gene expression
in signalling pathway: ligand + PM receptor–>ectodomain shedding (facilitated by members of metalloproteinase-disintegrin family, producing carboxyl terminal fragment that is the substrate for gamma secretase induces RIP releasing an Intracellular domain of the protein that enters nucleus and regulates transcription
e.g SREB (sterol regualtory element binding protein
SREB
sterol regulatory element binding protein
transmembrane protein in ER
if cellular cholesterol is HIGH, SREB undergoes RIP, and proteolytically cleaved fragment is translocated into nucleus where it transcriptionally activates genes that promote cholesterol biosynthesis***
*RIP (regulated intramembrane proteolysis)
