The adaptor proteins HAP1a and GRIP1 collaborate to activate kinesin-1 isoform KIF5C

Author:

Twelvetrees Alison E.1ORCID,Lesept Flavie2,Holzbaur Erika L. F.3ORCID,Kittler Josef T.2ORCID

Affiliation:

1. Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK

2. Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK

3. Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA

Abstract

Binding of motor proteins to cellular cargoes is regulated by adaptor proteins. HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein-complex in the brain, and co-operate to activate kinesin-1 subunit KIF5C in vitro. Based upon this co-operative activation of kinesin-1, we propose a modification to the kinesin activation model that incorporates stabilisation of the central hinge region known to be critical to autoinhibition of kinesin-1.

Funder

Medical Research Council

Wellcome Trust

National Institutes of Health

Publisher

The Company of Biologists

Subject

Cell Biology

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