title: Coordination of autophagosome-lysosome fusion and transport by a Klp98A-Rab14 complex in Drosophila.
abstract: Degradation of cellular material by autophagy is essential for cell survival and homeostasis, and requires intracellular transport of autophagosomes to encounter acidic lysosomes through unknown mechanisms. Here, we identify the PX-domain-containing kinesin Klp98A as a new regulator of autophagosome formation, transport and maturation in Drosophila. Depletion of Klp98A caused abnormal clustering of autophagosomes and lysosomes at the cell center and reduced the formation of starvation-induced autophagic vesicles. Reciprocally, overexpression of Klp98A redistributed autophagic vesicles towards the cell periphery. These effects were accompanied by reduced autophagosome-lysosome fusion and autophagic degradation. In contrast, depletion of the conventional kinesin heavy chain caused a similar mislocalization of autophagosomes without perturbing their fusion with lysosomes, indicating that vesicle fusion and localization are separable and independent events. Klp98A-mediated fusion required the endolysosomal GTPase Rab14, which interacted and colocalized with Klp98A, and required Klp98A for normal localization. Thus, Klp98A coordinates the movement and fusion of autophagic vesicles by regulating their positioning and interaction with the endolysosomal compartment.
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mauvezin
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Neisch
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Carlos I
authors.initials: CI
authors.lastname: Ayala
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Beltrame
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Braden
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Gardner
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hays
authors.affiliation: Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA neufe003@umn.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Neufeld
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000502:physiology*; D001343:Autophagy; D002460:Cell Line; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D016547:Kinesins / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D022161:Transport Vesicles / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000502:physiology*
chemical_list: C527373:Atg8a protein, Drosophila; D029721:Drosophila Proteins; D016547:Kinesins; C000612846:Klp98A protein, Drosophila; C000612845:Rab14 protein, Drosophila; D020691:rab GTP-Binding Proteins
keywords: Autophagy; Intracellular trafficking; Klp98A; Rab14