Neuronal Activity and CaMKII Regulate Kinesin-Mediated Transport of Synaptic AMPARs

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2015 Apr 7

PMID 25843407

Citations 49

Authors

Frederic J Hoerndli

Rui Wang

Jerry E Mellem

Angy Kallarackal

Penelope J Brockie

Colin Thacker

David M Madsen

Andres V Maricq

Affiliations

Soon will be listed here.

Abstract

Excitatory glutamatergic synaptic transmission is critically dependent on maintaining an optimal number of postsynaptic AMPA receptors (AMPARs) at each synapse of a given neuron. Here, we show that presynaptic activity, postsynaptic potential, voltage-gated calcium channels (VGCCs) and UNC-43, the C. elegans homolog of CaMKII, control synaptic strength by regulating motor-driven AMPAR transport. Genetic mutations in unc-43, or spatially and temporally restricted inactivation of UNC-43/CaMKII, revealed its essential roles in the transport of AMPARs from the cell body and in the insertion and removal of synaptic AMPARs. We found that an essential target of UNC-43/CaMKII is kinesin light chain and that mouse CaMKII rescued unc-43 mutants, suggesting conservation of function. Transient expression of UNC-43/CaMKII in adults rescued the transport defects, while optogenetic stimulation of select synapses revealed CaMKII's role in activity-dependent plasticity. Our results demonstrate unanticipated, fundamentally important roles for UNC-43/CaMKII in the regulation of synaptic strength.

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