components of intracellular signalling pathways Flashcards
what are the highly conserved signal transduction components of intracellular pathways?
protein kinases, phosphatases, cAMP, cGMP, G proteins, 1,2-Diacylglycerol, Ca2+, inositol 1,4,5-triphosphate (IP3)
what is the function of G proteins?
when activated by membrane receptors (G protein coupled receptors) they act as a GEF and trigger the release of GDP
what is the impact of GDP being bound to a G protein?
the protein is switched off
what is the impact of GTP being bound to a G protein?
it is switched on
how is a G protein switched on?
an activated receptor triggers the release of GDP, allowing GTP to bind as it has higher affinity. this causes conformational change which allow the G protein to bind to and activate other downstream signalling proteins.
what regulates G protein activation and ability to signal downstream?
GTPase activity
which G protein subunits are bound together in the resting state?
Ga, Gb, Gy
what happens to the G protein subunits when the protein is activated?
the a subunit dissociates and relays signals downstream
what are some stimulants of GCPRs?
hormones, ions, light, odorants, proteases
what are some functions of GCPRs?
neurotransmission, cell growth, vision, olfaction
how does a GPCR trigger a G protein response?
when a ligand binds the receptor changes conformation and binds to the Ga subunit. this causes Ga conformational change which causes GDP to dissociate. GTP binds and causes Ga to dissociate from the other subunits and bind to the effector. the hormone dissociates from the receptor and hydrolysis of GTP to GDP causes Ga dissociation from the effector and reassociation with the other subunits
how can the impact of adrenaline vary and what are some examples of this?
the impact of adrenaline can vary depending on the the effector domain of the receptor bound and the physiological function of the target cell. in the liver and adipose tissue it triggers the release of glucose and fatty acids
how do G proteins open K+ channels in the heart and what is the consequence of this?
acetylcholine binds to the muscarinic acetylcholine receptor in the heart, triggering the dissociation of a trimeric G protein. the Gby subunit directly binds to the K+ channel, opening it and causing cell polarisation and slowing of the heart rate
how do the rod cells detect light?
rod cells contain the GCPR rhodopsin which is coupled to the trimeric G protein transducin. In the dark the rods constantly release neurotransmitters, constantly stimulating the neurons as the rod membrane potential is about -30mV as the non-specific cation channels are activated in the dark. light activation causes the channels to close and the membrane potential becomes more negative and less neurotransmitter is released and this is perceived as light
how do rod cells adapt to high light levels?
when activated by light rhodopsin becomes a substrate for rhodopsin kinase which phosphorylates it, reducing its ability to activate transducin. when it is saturated with phosphorylation it is a substrate for arrestin and in this state it cannot activate transducin, reducing sensitivity to small changes in light. transducin moves from the outer segment of the cell to the inner segment and arrestin moves from the inner to the outer segment. this may involve microtubules and motor proteins
how can the impact of a ligand binding vary?
different receptor bound, inducing a different intracellular signal transduction pathway, different cell types
