A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation

Autor: Thomas S. Hays, Thomas P. Neufeld, Amanda L. Neisch
Rok vydání: 2017
Předmět:
0301 basic medicine
Autophagosome
Scaffold protein
Genotype
60410 Neurogenetics
Recombinant Fusion Proteins
Dynein
Presynaptic Terminals
Cellular homeostasis
Nerve Tissue Proteins
macromolecular substances
Biology
Transfection
Axonal Transport
Article
Cell Line
Animals
Genetically Modified
Motor protein
03 medical and health sciences
0302 clinical medicine
Animals
Drosophila Proteins
Protein Interaction Domains and Motifs
Protein Phosphatase 2
Research Articles
Adaptor Proteins
Signal Transducing
Secretory Vesicles
Autophagy
Autophagosomes
Dyneins
Cell Biology
Protein phosphatase 2
Axons
Cell biology
Drosophila melanogaster
Phenotype
030104 developmental biology
Microscopy
Fluorescence
Multiprotein Complexes
FOS: Biological sciences
Mutation
Axoplasmic transport
RNA Interference
030217 neurology & neurosurgery
Protein Binding
Signal Transduction
Zdroj: The Journal of Cell Biology
ISSN: 1540-8140
0021-9525
Popis: The regulation of cargo transport within neurons is not well understood. Neisch et al. use Drosophila genetics to identify a multiprotein STRIPAK complex required for autophagosome and dense core vesicle transport in neurons. PP2A activity within the complex is necessary for transport.
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.
Databáze: OpenAIRE
Externí odkaz: