title: Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour.
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.
authors.affiliation: Cancer Research UK Beatson Institute, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Tyrrell
authors.affiliation: Cancer Research UK Beatson Institute, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Emma F
authors.initials: EF
authors.lastname: Woodham
authors.affiliation: Cancer Research UK Beatson Institute, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Spence
authors.affiliation: Cancer Research UK Beatson Institute, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Strathdee
authors.affiliation: Cancer Research UK Beatson Institute, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Robert H
authors.identifier: 0000-0003-4898-040X
authors.initials: RH
authors.lastname: Insall
authors.affiliation: Cancer Research UK Beatson Institute, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. l.machesky@beatson.gla.ac.uk.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006200:Hair Color / Q000502:physiology*; D008297:Male; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D011506:Proteins; D033921:Vesicular Transport Proteins; C577014:WASH protein, mouse; C517003:WASHC5 protein, human
keywords: actin dynamics; endocytic trafficking; melanocytes; migration; vesicle traffic