Coordination of autophagosome-lysosome fusion and transport by a Klp98A-Rab14 complex in Drosophila

Caroline Mauvezin, Amanda L. Neisch, Carlos I. Ayala, Jung Kim, Abigail Beltrame, Christopher R. Braden, Melissa K. Gardner, Thomas S. Hays, Thomas P. Neufeld

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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. Klp98Amediated 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.

Original languageEnglish (US)
Pages (from-to)971-982
Number of pages12
JournalJournal of cell science
Volume129
Issue number5
DOIs
StatePublished - 2016

Bibliographical note

Funding Information:
We would like to thank Dr Michael O’Connor and Aidan Peterson for access and support for confocal microscopy. We are grateful to Sally Horne-Badovinac for providing the Rab10 and Rab11 constructs. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537), Drosophila Genetic Resource Center (Kyoto, Japan), FlyORF (Zurich Switzerland) and Vienna Drosophila Resource Center (VDRC) were used in this study.

Keywords

  • Autophagy
  • Intracellular trafficking
  • Klp98A
  • Rab14

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