Trafficking Kinesin Protein (TRAK)-mediated Transport of Mitochondria in Axons of Hippocampal Neurons

Brickley, K. and Stephenson, F.A. (2011) Trafficking Kinesin Protein (TRAK)-mediated Transport of Mitochondria in Axons of Hippocampal Neurons. Journal of Biological Chemistry, 286 (20). p. 18079. 10.1074/jbc.M111.236018.

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DOI: 10.1074/jbc.M111.236018

Abstract

In neurons, the proper distribution of mitochondria is essential because of a requirement for high energy and calcium buffering during synaptic neurotransmission. The efficient, regulated transport of mitochondria along axons to synapses is therefore crucial for maintaining function. The TRAK/Milton family of proteins are kinesin adaptors that have been implicated in the neuronal trafficking of mitochondria via their association with the mitochondrial protein, Miro, and kinesin motors. In this study, we have employed gene silencing by targeted shRNAi and dominant negative approaches in conjunction with live imaging to investigate the contribution of endogenous TRAKs, TRAK1 and TRAK2, to the transport of mitochondria in axons of hippocampal pyramidal neurons. We report that both strategies result in impairing mitochondrial mobility in axonal processes. Differences were apparent in terms of the contribution of TRAK1 and TRAK2 to this transport since knockdown of TRAK1 but not TRAK2 impaired mitochondrial mobility yet both TRAK1 and TRAK2 were shown to rescue transport impaired by TRAK1 gene knockout. Thus we demonstrate for the first time the pivotal contribution of the endogenous TRAK family of kinesin adaptors to the regulation of mitochondrial mobility.

Item Type:Article
Uncontrolled Keywords:Kinesin; Mitochondria; Mitochondrialtransport; Neurobiology; Trafficking
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2484
Journal or Publication Title:Journal of Biological Chemistry
Deposited By:Library Staff
Deposited On:18 Nov 2011 17:34
Last Modified:18 Nov 2011 17:34

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