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- Title
Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain.
- Authors
Dragich, Joanna M.; Takaaki Kuwajima; Megumi Hirose-Ikeda; Yoon, Michael S.; Eenjes, Evelien; Bosco, Joan R.; Fox, Leora M.; Lystad, Alf H.; Oo, Tinmarla F.; Olga Yarygina; Tomohiro Mita; Waguri, Satoshi; Yoshinobu Ichimura; Masaaki Komatsu; Simonsen, Anne; Burke, Robert E.; Mason, Carol A.; Ai Yamamoto
- Abstract
The regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the autophagic machinery, is highly expressed in the developing central nervous system, indicating that this pathway may have yet unexplored roles in neurodevelopment. To examine this possibility, we used mouse genetics to eliminate Alfy expression. We report that this evolutionarily conserved protein is required for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Consistent with a phenotype reflecting a failure in axon guidance, the loss of Alfy in mice disrupts localization of glial guidepost cells, and attenuates axon outgrowth in response to Netrin-1. These findings further support the growing indication that macroautophagy plays a key role in the developing CNS.
- Subjects
AUTOPHAGY; PROTEOLYSIS; CELLULAR signal transduction; UBIQUITINATION; PROTEIN expression
- Publication
eLife, 2016, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.14810