G protein-coupled receptors

Examples of G protein-coupled receptors in the following topics:

• Ionotropic and Metabotropic Receptors

  • Although both ionotropic and metabotropic receptors are activated by neurotransmitters, ionotropic receptors are channel-linked while metabotropic receptors initiate a cascade of molecules via G-proteins.
  • Two types of membrane-bound receptors are activated with the binding of neurotransmitters: ligand-gated ion channels (LGICs) inotropic receptors and metabotropic G- protein coupled receptors.
  • Metabotropic receptors are a subtype of membrane receptors that do not form an ion channel pore but use signal transduction mechanisms, often G proteins, to activate a series of intracellular events using second messenger chemicals.
  • The metabotropic G protein-coupled receptors have seven hydrophobic transmembrane domains.
  • When the neurotransmitter binds to the receptor, there is an activation via the G-protein that later activates the  secondary messengers.

• Adrenergic Neurons and Receptors

  • The adrenergic receptors (or adrenoceptors) are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine or noradrenaline, and epinephrine (adrenaline).
  • There are two main groups of adrenergic receptors, α and β, with several subtypes. α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a Gi coupled receptor).
  • All three are linked to Gs proteins (although β2 also couples to Gi), which in turn are linked to adenylate cyclase.
  • α1-adrenergic receptors are members of the G protein-coupled receptor superfamily.
  • On activation, a heterotrimeric G protein, Gq, activates phospholipase C (PLC).

• Direct Gene Activation and the Second-Messenger System

  • Most hormone receptors are G protein-coupled receptors.
  • Upon hormone binding, the receptor undergoes a conformational change and exposes a binding site for a G-protein.
  • The G-protein is bound to the inner membrane of the cell and consists of three sub-units: alpha, beta, and gamma.
  • Upon binding to the receptor, it releases a GTP molecule, at which point the alpha sub-unit of the G-protein breaks free from the beta and gamma sub-units and is able to move along the inner membrane until it contacts another membrane-bound protein: the primary effector. 
  • G-protein is activated and produces an effector. 3.

• Olfaction: The Nasal Cavity and Smell

  • Each functions using cilia, small hair-like projections that contain olfactory receptor proteins.
  • These proteins carry out the transduction of odorants into electrical signals for neural processing.
  • In mammals, olfactory receptors have been shown to signal via G protein.
  • This is a similar type of signaling of other known G protein-coupled receptors (GPCR).
  • The binding of an odorant particle on an olfactory receptor activates a particular G protein (Gαolf), which then activates adenylate cyclase, leading to cAMP production. cAMP then binds and opens a cyclic nucleotide-gated ion channel.

• Types of Receptors

  • G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein.
  • All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.
  • Cell signaling using G-protein-linked receptors occurs as a cyclic series of events.
  • Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which releases GDP and picks up GTP.
  • When a signaling molecule binds to a G-protein-coupled receptor in the plasma membrane, a GDP molecule associated with the α subunit is exchanged for GTP.

• Reception and Transduction

  • Humans have about 12 million olfactory receptors distributed among hundreds of different receptor types that respond to different odors.
  • The sensory receptors on the cilia are proteins.
  • When an odorant binds with a receptor that recognizes it, the sensory neuron associated with the receptor is stimulated.
  • Sour tastants are acids which belong to the thermoreceptor protein family.
  • Sweet, bitter, and umami tastants require a G-protein-coupled receptor.

• Gustation: Taste Buds and Taste

  • Bitter, sweet, and umami tastes use similar mechanisms based on a G protein-coupled receptor, or GPCR.
  • The salt receptor, NaCl, is arguable the simplest of all the receptors found in the mouth.
  • Synthetic sweeteners such as saccharin activate a separate set of GPCRs, initiating a similar but different process of protein transitions.
  • There are three different receptor proteins at work in a sour taste.
  • It is thought that umami receptors act similarly to bitter and sweet receptors (involving GPCRs), but very little is known about their actual function.

• Plasma Membrane Hormone Receptors

  • When a hormone binds to its membrane receptor, a G protein that is associated with the receptor is activated.
  • G proteins are proteins separate from receptors that are found in the cell membrane.
  • When a hormone is not bound to the receptor, the G protein is inactive and is bound to guanosine diphosphate, or GDP.
  • When a hormone binds to the receptor, the G protein is activated by binding guanosine triphosphate, or GTP, in place of GDP.
  • The binding of a hormone at a single receptor causes the activation of many G-proteins, which activates adenylyl cyclase.

• Binding Initiates a Signaling Pathway

  • Cell-surface receptors, also known as transmembrane receptors, are membrane-anchored (integral) proteins that bind to external ligand molecules.
  • There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.
  • G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein.
  • The activated G-protein then interacts with either an ion channel or an enzyme in the membrane.
  • All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.

• Mapping Protein-Protein Interactions

  • Mapping protein-protein interactions gives us a better understanding of molecular mechanisms inside the cell.
  • The protein complexes formed could be stable (proteins interact for a prolonged period of time) or transient (proteins interact for a brief period of time).
  • The most widely employed tools are the yeast two-hybrid system and affinity purification coupled to mass spectrometry.
  • If the two proteins do interact the bait recruits the prey to a specific cellular location where it can stimulate a detectable output (e.g., gene activation).
  • Affinity purification of protein complexes coupled to mass spectrometry is carried out as follows: a specific protein (the bait) is manipulated to express an affinity tag.