RRC ID 47665
Author Mauvezin C, Neisch AL, Ayala CI, Kim J, Beltrame A, Braden CR, Gardner MK, Hays TS, Neufeld TP.
Title Coordination of autophagosome-lysosome fusion and transport by a Klp98A-Rab14 complex in Drosophila.
Journal J Cell Sci
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.
Volume 129(5)
Pages 971-82
Published 2016-3-1
DOI 10.1242/jcs.175224
PII jcs.175224
PMID 26763909
PMC PMC4813314
MeSH Animals Autophagosomes / physiology* Autophagy Cell Line Drosophila Proteins / metabolism Drosophila Proteins / physiology* Drosophila melanogaster / cytology Drosophila melanogaster / metabolism* Kinesin / physiology* Lysosomes / physiology* Protein Binding Protein Transport Proteolysis Transport Vesicles / metabolism rab GTP-Binding Proteins / physiology*
IF 4.517
Times Cited 22