Presynaptic CaMKII Regulates Activity-Dependent Axon Terminal Growth

Publication Date

8-24-2016

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Biological Sciences

Keywords

CaMKII, Activity-dependent axon terminal growth, NMJ, miRNA pathway

Abstract

Spaced synaptic depolarization induces rapid axon terminal growth and the formation of new synaptic boutons at the Drosophila larval neuromuscular junction (NMJ). Here, we identify a novel presynaptic function for the Calcium/Calmodulin-dependent Kinase II (CamKII) protein in the control of activity-dependent synaptic growth. Consistent with this function, we find that both total and phosphorylated CamKII (p-CamKII) are enriched in axon terminals. Interestingly, p-CamKII appears to be enriched at the presynaptic axon terminal membrane. Moreover, levels of total CamKII protein within presynaptic boutons globally increase within one hour following stimulation. These effects correlate with the activity-dependent formation of new presynaptic boutons. The increase in presynaptic CamKII levels is inhibited by treatment with cyclohexamide suggesting a protein-synthesis dependent mechanism. We have previously found that acute spaced stimulation rapidly downregulates levels of neuronal microRNAs (miRNAs) that are required for the control of activity-dependent axon terminal growth at this synapse. The rapid activity-dependent accumulation of CamKII protein within axon terminals is inhibited by overexpression of activity-regulated miR-289 in motor neurons. Experiments in vitro using a CamKII translational reporter show that miR-289 can directly repress the translation of CamKII via a sequence motif found within the CamKII 3′ untranslated region (UTR). Collectively, our studies support the idea that presynaptic CamKII acts downstream of synaptic stimulation and the miRNA pathway to control rapid activity-dependent changes in synapse structure.

Copyright Date

8-24-2016

Copyright Statement / License for Reuse

All Rights Reserved
All Rights Reserved.

Rights Holder

Elsevier Inc.

Provenance

Received from author

Language

English (eng)

Extent

9 pgs

Publication Statement

Copyright is held by Elsevier Inc. User is responsible for all copyright compliance.

Publication Title

Molecular and Cellular Neuroscience

Volume

76

First Page

33

Last Page

41

ISSN

1095-9327

This document is currently not available here.

Find in Compass

Find in WorldCat

Share

COinS