Apr 10, 2020

PKD promotes activity-dependent AMPA receptorendocytosis in hippocampal neurons

BioRxiv : the Preprint Server for Biology
C. O. Oueslati MoralesAngelika Hausser

Abstract

AMPA type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the Protein Kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs and slowed down their endocytic trafficking. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their co-localization with early endosomes. On a molecular level, we identify PKD-mediated phosphorylation of the Rab5 effector protein Rabaptin-5 to be required for promoting activity-dependent AMPAR endocytosis. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

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