title: A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation.
abstract: Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion. In this study, we identify the scaffold protein CKA (connector of kinase to AP-1) as essential for autophagosome transport in neurons. Together with other core components of the striatin-interacting phosphatase and kinase (STRIPAK) complex, we show that CKA associates with dynein and directly binds Atg8a, an autophagosomal protein. CKA is a regulatory subunit of PP2A, a component of the STRIPAK complex. We propose that the STRIPAK complex modulates dynein activity. Consistent with this hypothesis, we provide evidence that CKA facilitates axonal transport of dense core vesicles and autophagosomes in a PP2A-dependent fashion. In addition, CKA-deficient flies exhibit PP2A-dependent motor coordination defects. CKA function within the STRIPAK complex is crucial to prevent transport defects that may contribute to neurodegeneration.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Amanda L
authors.identifier: http://orcid.org/0000-0002-3002-9221
authors.initials: AL
authors.lastname: Neisch
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Neufeld
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455 haysx001@umn.edu.
authors.forename: Thomas S
authors.identifier: http://orcid.org/0000-0002-4911-6042
authors.initials: TS
authors.lastname: Hays
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D000071182:Autophagosomes / Q000201:enzymology*; D001370:Axonal Transport; D001369:Axons / Q000201:enzymology*; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000201:enzymology*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527373:Atg8a protein, Drosophila; C499664:Cka protein, Drosophila; D029721:Drosophila Proteins; C549314:Mob4 protein, Drosophila; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C529534:mts protein, Drosophila; D054648:Protein Phosphatase 2; D004398:Dyneins