Journal
FEBS LETTERS
Volume 585, Issue 5, Pages 730-736Publisher
WILEY
DOI: 10.1016/j.febslet.2011.01.045
Keywords
ALS2; Rac1; Macropinosome; Endosome; Autophagosome; Amphisome
Funding
- Japan Society for the Promotion of Science (JSPS)
- Japan Science and Technology Agency
- Ministry of Health, Labor and Welfare
- Japan Amyotrophic Lateral Sclerosis Association
- Tokai University General Research Organization
- Tokai University School of Medicine Research Aid
Ask authors/readers for more resources
Loss of ALS2/alsin function accounts for several recessive motor neuron diseases. ALS2 is a Rab5 activator and its endosomal localization is regulated by Rac1 via macropinocytosis. Here, we show that the pathogenic missense ALS2 mutants fail to be localized to Rac1-induced macropinosomes as well as endosomes, which leads to loss of the ALS2 function as a Rab5 activator on endosomes. Further, these mutants lose the competence to enhance the formation of amphisomes, the hybrid-organelle formed upon fusion between autophagosomes and endosomes. Thus, Rac1-induced relocalization of ALS2 might be crucial to exert the ALS2 function associated with the autophagy-endolysosomal degradative pathway. Structured summary: Rac1 physically interacts with ALS2 by pull down (View interaction) Rab5A physically interacts with ALS2 by pull down (View Interaction 1, 2) ALS2 and EEA1 colocalize by fluorescence microscopy (View Interaction 1, 2, 3) ALS2 physically interacts with ALS2 by anti tag coimmunoprecipitation (View interaction) (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available