Upregulation of ?3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway.

ABSTRACT: Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved, we performed a cell-type-specific screen for transcripts persistently altered during scaling, which identified the ? subunit (?3A) of the adaptor protein complex AP-3A. Synaptic scaling increased ?3A (but not other AP-3 subunits) in pyramidal neurons and redistributed dendritic ?3A and AMPAR to recycling endosomes (REs). Knockdown of ?3A prevented synaptic scaling and this redistribution, while overexpression (OE) of full-length ?3A or a truncated ?3A that cannot interact with the AP-3A complex was sufficient to drive AMPAR to REs. Finally, OE of ?3A acted synergistically with GRIP1 to recruit AMPAR to the dendritic membrane. These data suggest that excess ?3A acts independently of the AP-3A complex to reroute AMPAR to RE, generating a reservoir of receptors essential for the regulated recruitment to the synaptic membrane during scaling up.

SUBMITTER: Steinmetz CC 

PROVIDER: S-EPMC5226429 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature