{"id":{"repo_id":"birmingham","oai_identifier":"oai:etheses.bham.ac.uk:1550"},"canonical_url":"https://search.dev.ndltd.org/etd/birmingham/oai:etheses.bham.ac.uk:1550","repository":{"repo_id":"birmingham","name":"University of Birmingham","base_url":"https://etheses.bham.ac.uk/cgi/oai2"},"display":{"title":"Identifying a role for WASH in the endocytic pathway of Dictyostelium discoideum","abstract":"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.","abstract_html":"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.","abstract_has_math":true,"creators":["Carnell, Michael John"],"institution":"University of Birmingham","degree_name":"d_ph","degree_level":"d_ph","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-07","date_published":"2011-07","updated_at":"2026-07-24T01:11:37Z","subjects":["QR Microbiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["na"]},{"key":"dc:creator","label":"Author","values":["Carnell, Michael John"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-07"]},{"key":"dc:date.issued","label":"Date","values":["2011-07"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["College of Life & Environmental Sciences","School of Biosciences"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Birmingham"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["http://etheses.bham.ac.uk//id/eprint/1550/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["d_ph"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["d_ph"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["QR Microbiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://etheses.bham.ac.uk//id/eprint/1550/1/Carnell_11_PhD.pdf","http://etheses.bham.ac.uk//id/eprint/1550/2/Decl_IS_Carnell_11_PhD.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Identifying a role for WASH in the endocytic pathway of Dictyostelium discoideum"]}]}],"canonical_facts":{"dc:contributor.sponsor":["na"],"dc:creator":["Carnell, Michael John"],"dc:date":["2011-07"],"dc:date.issued":["2011-07"],"dc:description.abstract":["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. 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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."],"dc:format":["application/pdf"],"dc:identifier.uri":["http://etheses.bham.ac.uk//id/eprint/1550/1/Carnell_11_PhD.pdf","http://etheses.bham.ac.uk//id/eprint/1550/2/Decl_IS_Carnell_11_PhD.pdf"],"dc:publisher.department":["College of Life & Environmental Sciences","School of Biosciences"],"dc:publisher.institution":["University of Birmingham"],"dc:relation.isreferencedby":["http://etheses.bham.ac.uk//id/eprint/1550/"],"dc:subject":["QR Microbiology"],"dc:title":["Identifying a role for WASH in the endocytic pathway of Dictyostelium discoideum"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["d_ph"],"dc:type.qualificationname":["d_ph"]},"updated_at":"2026-07-24T01:11:37Z"}