Abstract
Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses in both basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 specifically promotes exocytosis of newly synthesised GluA2-containing AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with AP-4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking. In addition, it provides a possible mechanism for the intellectual disability symptoms that occur in AP-4 deficiency syndrome.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Impact statement In mature neurons, TSPAN5 assembles a complex with AP-4 and Stargazin to promote the exocytosis of newly synthesised GluA2-containing AMPA receptors.
