Letter abstract
Nature Cell Biology 9, 176 - 183 (2006)
Published online: 24 December 2006 | doi:10.1038/ncb1531
Myosin VI targeting to clathrin-coated structures and dimerization is mediated by binding to Disabled-2 and PtdIns(4,5)P2
Giulietta Spudich1, Margarita V. Chibalina2, Josephine Sui-Yan Au1, Susan D. Arden2, Folma Buss2 & John Kendrick-Jones1
Vesicle transport is essential for the movement of proteins, lipids and other molecules between membrane compartments within the cell. The role of the class VI myosins in vesicular transport is particularly intriguing because they are the only class that has been shown to move 'backwards' towards the minus end of actin filaments1. Myosin VI is found in distinct intracellular locations and implicated in processes such as endocytosis2, 3, exocytosis, maintenance of Golgi morphology4, 5 and cell movement6. We have shown that the carboxy-terminal tail is the key targeting region and have identified three binding sites: a WWY motif for Disabled-2 (Dab2) binding, a RRL motif for glucose-transporter binding protein (GIPC) and optineurin binding and a site that binds specifically and with high affinity (Kd = 0.3 
M) to PtdIns(4,5)P2-containing liposomes. This is the first demonstration that myosin VI binds lipid membranes. Lipid binding induces a large structural change in the myosin VI tail (31% increase in helicity) and when associated with lipid vesicles, it can dimerize. In vivo targeting and recruitment of myosin VI to clathrin-coated structures (CCSs) at the plasma membrane is mediated by Dab2 and PtdIns(4,5)P2 binding.
- MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
- Cambridge Institute for Medical Research, University of Cambridge, Wellcome/MRC Building, Hills Road, Cambridge CB2 2XY, UK.
Correspondence to: John Kendrick-Jones1 e-mail: jkj@mrc-lmb.cam.ac.uk
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