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Dev Cell. 2011 Dec 13;21(6):1171-8. doi: 10.1016/j.devcel.2011.10.007.

Arl8 and SKIP act together to link lysosomes to kinesin-1.

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1
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

Abstract

Lysosomes move bidirectionally on microtubules, and this motility can be stimulated by overexpression of the small GTPase Arl8. By using affinity chromatography, we find that Arl8-GTP binds to the soluble protein SKIP (SifA and kinesin-interacting protein, aka PLEKHM2). SKIP was originally identified as a target of the Salmonella effector protein SifA and found to bind the light chain of kinesin-1 to activate the motor on the bacteria's replicative vacuole. We show that in uninfected cells both Arl8 and SKIP are required for lysosomes to distribute away from the microtubule-organizing center. We identify two kinesin light chain binding motifs in SKIP that are required for lysosomes to accumulate kinesin-1 and redistribute to the cell periphery. Thus, Arl8 binding to SKIP provides a link from lysosomal membranes to plus-end-directed motility. A splice variant of SKIP that lacks a light chain binding motif does not stimulate movement, suggesting fine-tuning by alternative splicing.

PMID:
22172677
PMCID:
PMC3240744
DOI:
10.1016/j.devcel.2011.10.007
[Indexed for MEDLINE]
Free PMC Article
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