PUBLICATION

Arf6 and the 5'phosphatase of Synaptojanin 1 regulate autophagy in cone photoreceptors

Authors
George, A.A., Hayden, S., Stanton, G.R., Brockerhoff, S.E.
ID
ZDB-PUB-160429-5
Date
2016
Source
Inside the cell   1: 117-133 (Journal)
Registered Authors
Brockerhoff, Susan
Keywords
Arf6, Synaptojanin1, autophagy, neuron, phosphoinositides, photoreceptor, zebrafish
MeSH Terms
none
PubMed
27123470 Full text @ Inside Cell
Abstract
Abnormalities in the ability of cells to properly degrade proteins have been identified in many neurodegenerative diseases. Recent work has implicated Synaptojanin 1 (SynJ1) in Alzheimer's disease and Parkinson's disease, although the role of this polyphosphoinositide phosphatase in protein degradation has not been thoroughly described. Here we dissected in vivo the role of SynJ1 in endolysosomal trafficking in zebrafish cone photoreceptors using a SynJ1-deficient zebrafish mutant, nrca14 . We found that loss of SynJ1 leads to specific accumulation of late endosomes and autophagosomes early in photoreceptor development. An analysis of autophagic flux revealed that autophagosomes accumulate due to a defect in maturation. In addition we found an increase in vesicles that are highly enriched for PI(3)P, but negative for an early endosome marker in nrca14 cones. A mutational analysis of SynJ1 enzymatic domains found that activity of the 5' phosphatase, but not the Sac1 domain, is required to rescue both aberrant late endosomes and autophagosomes. Finally, modulating activity of the PI(4,5)P2 regulator, Arf6, rescued the disrupted trafficking pathways in nrca14 cones. Our study describes a specific role for SynJ1 in autophagosomal and endosomal trafficking and provides evidence that PI(4,5)P2 participates in autophagy in a neuronal cell type.
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