G Protein Couple Receptors and Second Messengers Flashcards
(35 cards)
What are the main types of second messenger ?
- Cyclic nucleotides (e.g. cGMP, cAMP
- Lipid messengers
- Ions (e.g. calcium)
- Endogenous gases (e.g. Nitric oxide)
What are the different types of cellular receptors?
- Intracellular Receptors
- Membrane Receptors
- Ionotropic receptors
- Catalytic receptors
- G protein coupled receptors
What are some components of G protein signalling cascade ?
- GPCR (discriminator)
- G protein (transducer)
- Effector (amplifier)
- Secondary messenger
What are some examples of G protein coupled receptors and explain?
- Opioid receptors
- Opium is produced from the opium poppy and contains over 20 alkaloids including morphine. Morphine manifestsIts action through the activation of opioid receptors - Muscarinic cholinergic receptors
- Muscarine was first isolated from the mushroom Amanita muscaria. Some of the toxic effects of this mushroom are caused by the action of muscarine on muscarinic receptors - Cannabinoid receptors
- Cannabis contains 61 different alkaloids. Cannabinoid receptors are present almost everywhere in the CNS2
What are the structures of GPCRs ?
- Two-dimensional model of GPCRs
- X-ray structure of Rhodopsin
Classification of GPCRS: Family 1
- Catecholamines (adrenaline, noradrenaline, dopamine) - mediate so-called fight-or-flight response.
- Cytokines - are involved in the regulation of differentiation and survival of neural cells
- Glycoprotein hormones - are the most chemically complex family of the peptide hormones. Some of them are produced in the CNS.
Classification of GPCRS: Family 2
Secretine - is a peptide hormone consisting of27 amino acids. It is likely to be involved in learning and memory.
Classification of GPCRS: Family 3
GABA - is a major inhibitory neurotransmitter in the CNS.Glutamate is the most common excitatory neurotransmitter in the CNS.
Classification of GPCRS: Family 4
Pheromone receptors
Classification of GPCRS: Family 5
Cyclic AMP receptor–like receptors
Classification of GPCRS: Family 6
Frizzled receptors
Explain obligatory hetero-dimerization?
Heterodimerization of two protomers is required to form functional receptors
Explain non-obligatory hetero-dimerization? ?
Heterodimers are composed of the functional GPCR promoters
Explain homo-dimerization?
The interaction between GPCR monomers might serve as a mechanism for signal amplification
What is GABA ?
GABA (g-aminobutiric acid) is a major inhibitory neurotransmitter in the CNS
Explain the structure of functional GABAb receptors ?
- The functional GABAb receptor is a constitutive dimer formed between GABAbR1 and GABAbR2
- When expressed alone, the GABABR1 is retained in the endoplasmic reticulum (ER) because of the presence of an ER-retention sequence in the C-terminal tail
- Co-expression of the GABABR2 results in the retention motif being masked and allows delivery of the dimer
What are G proteins ?
G proteins are globular proteins found on the inside of the cell membrane. They have been called ‘G proteins’ because of their ability to bind either Guanosine diphosphate (GDP) or Guanosine triphosphate (GTP)
Explain the receptor-dependent activation of G proteins ?
- The α subunit bound to GDP interacts with the βγ dimer to form G protein in its inactive resting state
- Binding of an agonist stabilises the active conformation of GPCRs. This uncovers previously masked G protein-binding sites
- When bound to a GPCR, the G protein undergoes important conformational changes. This provokes the dissociation of GDP from the α subunit
- GTP binding induces changes in the conformation within subunit. Activated α subunit dissociates from the receptor and the βγ dimer
- Free activated α subunit and βγ dimer can now modulate activities of many targets in the cell.
Indirect actions of activated G proteins are mediated by?
Primary effectors
Cellular responses caused by indirect actions are ?
Slower than those caused by the direct interaction between G protein subunits and ion channels
What do activation of effector proteins lead to ?
Significant amplification of the signal
Different types of α subunits interact in a highly specific manner with effector protein. Name them and what they do ?
- αs stimulates Adenylyl cyclase
- αi inhibits Adenylyl cyclase
- αq activates Phospholipase C
- α12 & α13 activate Rho
- αt activates cGMP-phosphodiesterase
What does Adenylate cyclase contain ?
Adenylate Cyclase contains two hydrophobic domains each consisting of 6 transmembrane segments separated by a large (40 kDa) cytoplasmic loop
What does cAMP activate?
cAMP-dependent protein kinase (PKA)
