Question

describe the role of stargazin and its involvement in AMPA and NMDA receptors trafficing in dendrites

Answer 1

Change in synaptic strength can modulate the capacity of learning and memory. This variability of synaptic strength is modulated by the neuronal gene expression. Both the AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor and the NMDA (N-methyl-D aspartate) receptor are the glutamate receptor that play a significant role in the regulation of synaptic strength. The short term changes in synaptic strength is attributed by the AMPA receptor, while NMDA receptor contributes long term maintenance of synaptic changes. Glutamate binding to the AMPA receptor promotes its conformation changes, as a result channel became open and permit Na+ and K+ to flow through and depolarization of the synaptic membrane occurs. When this depolarization reached at 30 mV, and in the presence of glutamate and glycine, NMDA receptors are activated, and allow the Na+, K+ and Ca+ to flow through. The exocytosis and endocytosis of postsynaptic AMPA receptors regulates the long-lasting synaptic plasticity in the form of long term potentiation (LTP) and long term depression (LTD) respectively. During trafficking of membrane proteins, cargo proteins are sorted via different adapter proteins (AP), such as AP1, AP2, AP3 and AP4. The endocytosis of AMPA receptor is regulated by one of its regulatory protein, known as stargazin. Based on the phosphorylation status of stargazin, it forms a ternary complex with the AP2 and AP3A. NMDA receptor mediated activation of calcineurin dephosphorylates the stargazin. This dephosphorylation of stargazin promotes the formation of a complex engaging the AMPK receptor, the subunits of AP complex, AP2 and AP3A. The interaction between stargazin and AP2 was essential for NMDA-induced AMPA receptor endocytosis, and that between AP3A and stargazin was needed for the subsequent late endosome/lysosome trafficking of AMPA receptors to prevent them from recycling to the cell surface