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Identifying a role for WASH in the endocytic pathway of Dictyostelium discoideum

Carnell, Michael John (2011)
Ph.D. thesis, University of Birmingham.

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Members of the WASP protein family are direct activators of the arp2/3 complex, thereby regulating the nucleation of branched actin assemblies within the cell. Each sub-class possesses a unique N-terminal domain architecture allowing a division of labour between its members, each coupling different signal transduction pathways to the nucleation of specific actin structures. WASH (WASP and SCAR homologue) is a newly identified member of the WASP protein family. Due to its disruption in \(Drosophila\) proving lethal (Linardopopoulou et al., 2007) little is know as to the functional role of WASH at the cellular level. Other than it is important in the development of multicellular organisms. Here we successfully disrupt WASH in the single celled amoebae \(Dictyostelium\) \(discoideum\) and discover a role for WASH in the endocytic pathway. WASH was shown to be essential for the trafficking of indigestible material through the endocytic pathway, with its disruption causing a complete bock in cellular defecation. This was shown to be due to a defect in lysosomal maturation into neutral post-lysosomes. Using fluorescently tagged fusion proteins we show that WASH recruitment coincides with removal of the Vacuolar H+ ATPase from lysosomal membranes, and suggests a possible role for WASH and actin in regulating the luminal pH of intracellular compartments.

Type of Work:Ph.D. thesis.
Supervisor(s):Insall, Robert
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
ID Code:1550
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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