Cellular Communication (social cells) Flashcards
How can ligands be released into EC space?
- exocytosis
- diffusion
- expressed on cell surface
2x types of communication
-SHORT DISTANCE
- LONG DISTANCE
Types of short distance communication
- contact-dependent; eg. immune response
- autocrine signalling; proteins, RNAs etc. SELF
- paracrine signalling “ BESIDE
Types of long-distance communication
-synaptic; neurotransmitters
- endocrine; hormones
ENDOCRINE SIGNALLING
- long distance
- ligands are hormones
- lipophilic
- very specific targeting
PARACRINE SIGNALLING
short distance
- vast range of ligands; eg. growth factors, gases
- conc. of ligand is low and can be controlled with enzymes, ECM, antagonists and inhibitors
AUTOCRINE SIGNALLING
- cell signals to itself
- ligands include cytokines, growth factors and hormones
CONTACT-DEPENDENT SIGNALLING
THREE FORMS;
- membrane proteins interact on each cell
- membrane proteins interact with part of extracellular matrix
- junctions link cells allowing small molecules to pass
SYNAPTIC SIGNALLING
- rapid long-distance signalling
- very specific
- electrical impulses converted to chemical signal
How does extracellular signal convert into intracellular response?
- most ligands bind to receptors
- ligand-receptor interaction causes a conformational change in the receptor
- ## need to express correct receptor; competent cell
Four types of receptors
- Ion-channel coupled receptors; (ionotropic receptors)
- G-protein-coupled receptors; metabotropic transmission
- Enzyme-coupled reactors (eg. RTKs)
- Nuclear receptors
Glucose ion pump
- coupled with sodium uptake
- co-transporter
Calcium ion pump
- cytosolic conc. needs to be kept low
- uses ATP
- sodium
four types of ion channels
- ligand-gated
- voltage-gated
- leak channels
- stretch-activated
LIGAND GATED CHANNELS
- ligand binds to receptor
- opens the channel
- ions ( Na+, K+, Cl-) move through
VOLTAGE GATED CHANNELS
- resting potential of membrane; channel is closed
- depolarisation; gate opens
Resting membrane potential
- not the same as action potential
- the potential across the membrane where there is no AP being propagated
G protein-coupled receptors structure
- Belong to one of 3 families A, B or C
- 7 transmembrane helix structures
G proteins
- have 3 subunits; alpha, beta and gamma
- at rest; exists as a trimer where GDP is bound to the alpha subunit
- g-protein is tethered to the cell membrane by the alpha and gamma subunit
GPCR activation & inactivation
- Ligand binds to the GPCR @ ligand binding site
- causes a conformational change in the receptor
- causes a conformational change in the G protein
- GDP dissociates and is replaced by intracellular GTP
- alpha-GTP and beta-gamma complexes dissociate from receptor
- GTP is hydrolysed to GDP by GTPase
Types of G protein
G alpha (s)
G alpha (i)
G alpha (o)
G alpha (q)
Roles of G alpha (s) and G alpha (i)
Stimulation and inhibition of adenyl cyclase
-which converts ATP to cyclic AMP
cAMP activates kinases
Role of G alpha (q)
Stimulate phospholipase C
- involved in the release of intracellular Ca2+
Enzyme-linked receptors
- a major role in growth & cell division, immune response
- main types; RTKs, receptor serine/threonine kinases
or cytokine receptors - structure; large extracellular binding domain, connected by single membrane spanning alpha-helix to intracellular domain
Kinase-linked receptor activation & inactivation
- ligand binds to the receptor leads to dimerisation
- association between 2 intracellular domains creates active kinase enzyme
- tyrosine residues are phosphorylated
- these residues act as docking sites for other intracellular relay proteins
- cascade leads to biological effect
- terminated by tyrosine phosphatases
Classes of nuclear receptor by action mechanism
Class I; binds to ligand in the cytoplasm, form homodimers
Class II; in nucleus, form heterodimers
Receptor homeostasis
- Autologous; the conc. of the receptor can increase or decrease upon activation
- Heterologous; the conc. of the receptor can change upon activation of other nuclear receptors
