کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2048238 | 1074072 | 2011 | 7 صفحه PDF | دانلود رایگان |
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 summaryRac1 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)
Journal: FEBS Letters - Volume 585, Issue 5, 9 March 2011, Pages 730–736