title: The nuclear protein Waharan is required for endosomal-lysosomal trafficking in Drosophila.
abstract: Here we report Drosophila Waharan (Wah), a 170-kD predominantly nuclear protein with two potential human homologues, as a newly identified regulator of endosomal trafficking. Wah is required for neuromuscular-junction development and muscle integrity. In muscles, knockdown of Wah caused novel accumulations of tightly packed electron-dense tubules, which we termed 'sausage bodies'. Our data suggest that sausage bodies coincide with sites at which ubiquitylated proteins and a number of endosomal and lysosomal markers co-accumulate. Furthermore, loss of Wah function generated loss of the acidic LysoTracker compartment. Together with data demonstrating that Wah acts earlier in the trafficking pathway than the Escrt-III component Drosophila Shrb (snf7 in Schizosaccharomyces pombe), our results indicate that Wah is essential for endocytic trafficking at the late endosome. Highly unexpected phenotypes result from Wah knockdown, in that the distribution of ubiquitylated cargos and endolysosomal morphologies are affected despite Wah being a predominant nuclear protein. This finding suggests the existence of a relationship between nuclear functions and endolysosomal trafficking. Future studies of Wah function will give us insights into this interesting phenomenon.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester, UK.
authors.forename: Mohiddin
authors.initials: M
authors.lastname: Lone
authors.forename: Theresa
authors.initials: T
authors.lastname: Kungl
authors.forename: Andre
authors.initials: A
authors.lastname: Koper
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bottenberg
authors.forename: Richard
authors.initials: R
authors.lastname: Kammerer
authors.forename: Melanie
authors.initials: M
authors.lastname: Klein
authors.forename: Sean T
authors.initials: ST
authors.lastname: Sweeney
authors.forename: Richard P
authors.initials: RP
authors.lastname: Auburn
authors.forename: Cahir J
authors.initials: CJ
authors.lastname: O'Kane
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokop
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000502:physiology*; D054875:Ubiquitination; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C553663:NSL1 protein, Drosophila; D009687:Nuclear Proteins; C083890:SNF7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins