Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour

Tyrrell, B. J., Woodham, E. F., Spence, H. J., Strathdee, D., Insall, R. H. and Machesky, L. M. (2016) Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour. Pigment Cell and Melanoma Research, 29(5), pp. 559-571. (doi:10.1111/pcmr.12506) (PMID:27390154) (PMCID:PMC5082549)

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Abstract

The five-subunit WASH complex generates actin networks that participate in endocytic trafficking, migration and invasion in various cell types. Loss of one of the two subunits WASH or strumpellin in mice is lethal, but little is known about their role in mammals in vivo. We explored the role of strumpellin, which has previously been linked to hereditary spastic paraplegia, in the mouse melanocytic lineage. Strumpellin knockout in melanocytes revealed abnormal endocytic vesicle morphology but no impairment of migration in vitro or in vivo and no change in coat colour. Unexpectedly, WASH and filamentous actin could still localize to vesicles in the absence of strumpellin, although the shape and size of vesicles was altered. Blue native PAGE revealed the presence of two distinct WASH complexes, even in strumpellin knockout cells, revealing that the WASH complex can assemble and localize to endocytic compartments in cells in the absence of strumpellin.

Item Type:Articles
Additional Information:The authors acknowledge funding for this project from Cancer Research UK Core funding to LMM (A15673), RHI (A15672) and to the Biological Services Unit (A17196).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura and Strathdee, Dr Douglas and Insall, Professor Robert and Tyrrell, Mr Benjamin and Spence, Dr Heather
Authors: Tyrrell, B. J., Woodham, E. F., Spence, H. J., Strathdee, D., Insall, R. H., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Pigment Cell and Melanoma Research
Publisher:Wiley
ISSN:1755-1471
ISSN (Online):1755-148X
Published Online:12 September 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Pigment Cell and Melanoma Research 29(5): 559-571
Publisher Policy:Reproduced under a Creative Commons License

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