Molecular Signalling Flashcards
Essential components of intercellular communication
- signalling cell
- signal
- receptor
- target molecule
- response
Forms of intercellular communication
- synaptic
- paracrine
- endocrine
Types of signals mediating intercellular communication
- signalling molecules can be
- cell-impermeant (cant diffuse through cell - need receptors on post cell)
- cell permeant (can diffuse through post cell)
- cell-associated (signalling molecule is attached to pre cell)
Mechanisms of target protein regulation
- protein targets of signalling cascades are often phosphorylated on SERINE, THREONINE, or TYROSINE residues
- by Ser/Thr kinases and Tyrosine kinases
- phosphorylation leads to changes in protein structure or ability of protein to bind other proteins (changes its function)
- dephosphorylation by protein phosphatases reverses change
Ionotropic receptors
- ligand gated ion channels
- binding of ligand causes channel to open
- channel is ion selective
- diffusion of ions in/out of cytoplasm elicits change in membrane potential
- if ion channel permeable to calcium, calcium signalling initiated
Ionotropic receptor structure
- 4-5 subunits grouped around a central pore
- charged amino acid residues at pore entrance form ion selectivity filter
- gate in pore center opens with ligand binding
- DESENSITIZATION: closing when ligand is bound for long time
Metabotropic receptors
=GPCRs
- bind heterotrimeric G proteins
- binding of ligand = signal and activated the G protein
- G protein regulates enzymes and ion channels
Metabotropic receptor structure
- common structure: 7 transmembrane receptors
- ligand binding leads to conformational change in receptor that leads to replacement of GDP for GTP in G protein
Enzyme linked receptors
- have an intracellular domain that is enzymatically active
- Receptor Tyrosine Kinases
- Ser/Thr kinases
- Tyrosine and S/T phosphatases
- Guanylyl cyclases
-signalling binding to extracellular domain activates enzyme activity
Enzyme linked receptor: RTK
- activation of RTC involves:
- Ligand binding
- Receptor DIMERIZES (2 halves come together with NGF dimer as ligand
- Autophosphorylation
- Binding of effectors, phosphorylation of other proteins
Intracellular receptors
- activated by lipophilic signalling molecules that diffuse across PM
- binding of signalling molecule causes disinhibition of receptor (activates it) by dissociation of inhibitory protein
- cytosolic receptors translocate the receptor to the nucleus
- the activator receptors bind co-activator proteins and/or DNA to induce GENE TRANSCRIPTION
Properties of G Proteins
- able to bind and hydrolyze GTP
- regulate effectors (enzymes or ion channels)
- only interact with effectors when GTP bound
- inactive in GDP bound form
Classes of G proteins
- heterotrimeric:
- composed of 3 subunits (a, B, Y)
- activated by METABOTROPIC receptors
- small monomeric:
- single polypeptides
- activation by RECEPTOR TYROSINE KINASES
Activation/Inactivation of heterotrimeric G proteins
- ligand binds to GPCR
- GPCR promotes exchange of GDP for GTP
- G protein a subunit dissociated from BY subunit and leaves receptor
- Both a and BY subunit can interact with effectors
- GTPase activating protein (GAP) facilitated GTP hydrolysis (turning a unit back to GDP bound)
- Subunits reassociate with GPCR
Types and targets of heterotrimeric G proteins
Gs: activates adenylate cyclase
-increases cAMP production
Gi: inhibits adenylate cyclase
-decrease cAMP production
Gq: activates phospholipase C (PLC)
-increase diacyclglycreol and IP3 production
Gt (transducin): activates cGMP phosphodiesterase (PDE)
-decrease cGMP
