Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain

eLife

Megumi Hirose-Ikeda¹  Tinmarla F Oo²  Masaaki Komatsu³  Joan R Bosco⁴  Michael S Yoon⁴  Satoshi Waguri⁴  Evelien Eenjes⁴  Joanna M Dragich⁴  Tomohiro Mita⁴  Leora M Fox⁴  Ai Yamamoto⁴  Alf H Lystad⁴  Takaaki Kuwajima⁵  Olga Yarygina⁶  Carol A Mason⁶  Anne Simonsen⁷  Robert E Burke⁷  Yoshinobu Ichimura⁷ 

[1] Department of Cell Biology, College of Physicians and Surgeons, Columbia University, New York, United States;Doctoral Program in Neurobiology and Behavior, Columbia University, New York, United States;Department of Anatomy and Histology, Fukushima Medical University School of Medicine, Fukushima, Japan;Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, United States;Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, United States;Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;The Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;

关键词: Autophagy;    Alfy;    axon guidance;    corpus callosum;    neurodevelopment;    Wdfy3;   

DOI  :  10.7554/eLife.14810

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown