Transmembrane Receptors (HL) (HL IB Biology)

• A key neurotransmitters used throughout the nervous system is acetylcholine (ACh)
• Synapses that use the neurotransmitter ACh are known as cholinergic synapses
• Acetylecholine can bring about a change in membrane potential, meaning that it can reverse the charge across a nerve cell membrane
  
  • Membrane potential is also referred to as the voltage across a membrane
• The mechanism by which ACh changes membrane potential in neurones is as follows:
  • The arrival of a nerve impulse, or action potential, at the presynaptic membrane stimulates release of ACh into the synaptic cleft
  • The ACh molecules diffuse across the synaptic cleft and temporarily bind to ligand-gated sodium ion channels in the postsynaptic membrane
    • These channels are specialised transmembrane receptors
  • This causes a shape change in the sodium ion channel, which then opens, allowing positively charged sodium ions (Na⁺) to diffuse down a gradient into the cytoplasm of the postsynaptic neurone
  • The sodium ions reverse the charge across the postsynaptic membrane, initiating a new nerve impulse in the postsynaptic cell
  • ACh molecules are then broken down, using enzyme acetylcholinesterase, to prevent continued stimulation
  • The products are absorbed back into the presynaptic membrane, recycled and packaged into vesicles ready to be used when another action potential arrives

Acetylcholine receptor diagram

Acetylcholine binds to receptors on ligand-gated sodium ion channels, opening the channels and allowing Na+ ions to diffuse into nerve cells; this reverses membrane potential

• A G-protein-coupled-receptor (GPCR) is a transmembrane receptor protein responsible for the activation of a special intracellular protein molecule called a G-protein, which then initiates changes inside a cell
  • GPCRs are the largest and most diverse groups of membrane receptors in eukaryotes
• G-proteins are specialised proteins that bind to either GTP or GDP; they act as a switch, being activated or deactivated by signals at the membrane surface
  • GTP = guanine triphosphate (active G proteins)
  • GDP = guanosine diphosphate (inactive G-proteins)
  • These molecules are very similar to ATP, but contain guanine rather than adenine
• Inactive G-proteins are attached to the internal side of a GPCR, and are bound to GDP
• Signal transduction involves the activation of G-proteins as follows:
  
  • A non-steroid ligand binds to the GPCR on the outside of a cell
  • A conformational, or shape, change occurs which activates the attached G-protein
  • GTP replaces GDP on the G-protein, which then dissociates from the GPCR in two parts:
    • A GTP-bound alpha subunit
    • A beta-gamma dimer
  • Once dissociated, these subunits can interact with other membrane proteins, and can cause the release of second messengers
• Some of the targets of the activated G protein include
  • Enzymes 
  • Ion channels
• G-proteins return to their inactive state when GTP is hydrolysed to GDP and they associate once again with the GPCR

G-protein activation diagram

G-proteins are activated when a ligand binds to a GPCR on the cell surface membrane. When activated, GDP is replaced by GTP and the G-protein dissociates and interacts with other proteins in the cell membrane.

What is a receptor tyrosine kinase?

• Receptor tyrosine kinases (RTKs) are a class of transmembrane receptors responsible for many different signal transduction pathways and cellular responses
• An RTK is activated by a ligand on the external region of the cell membrane where the binding site is found
• After binding, the intracellular portion of the receptor becomes phosphorylated using phosphate groups from ATP
• This activated RTK then stimulates the assembly of relay proteins which are responsible for the onward signal transduction pathway
• One RTK can trigger multiple different signal transduction pathways simultaneously

The action of insulin

• Insulin is a hormone which triggers an increased uptake of glucose in target cells such as fat storage cells, adipose cells, muscle cells and liver cells
• RTKs in the cell membranes of these target cells are activated when insulin binds to the extracellular binding site
• This triggers the phosphorylation of tyrosine which then stimulates production of relay proteins
• The relay proteins then cause vesicles containing glucose transporter proteins in the cell cytoplasm to fuse to the cell surface membrane, adding more glucose transporter proteins to the membranes
  • This increases the permeability of the cells to glucose
  • The rate of facilitated diffusion of glucose into the cell increases

Insulin and tyrosine kinase diagram

Insulin binds to RTKs, resulting in the phosphorylation of tyrosine and a series of reactions that end with the fusion of vesicles that contain glucose transporter proteins with the cell surface membrane