ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome dynamics
- 作者：Kyoko Suzuki-Utsunomiya ; Shinji Hadano ; Asako Otomo ; Ryota Kunita ; Hikaru Mizumura ; Hitoshi Osuga ; Joh-E Ikeda
- 关键词：ALS2CL ; ALS2 ; Rab5 ; Guanine-nucleotide exchange factor (GEF) ; Endosome ; Motor neuron disease ; Interacting protein
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：9 March 2007
- 卷：354
- 期：2
- 页码：491-497
- 文件大小：591 K
摘要
ALS2, the causative gene product for a number of recessive motor neuron diseases, is a guanine-nucleotide exchange factor for Rab5, and acts as a modulator for endosome dynamics. Recently, we have identified a novel ALS2 homolog, ALS2CL, which is highly homologous to the C-terminal half of ALS2. In this study, we investigate the molecular features of ALS2CL and its functional relationship with ALS2. A majority of ALS2CL is present as a homo-dimeric form, which can interact with the ALS2-oligomer, resulting in the formation of the large ALS2/ALS2CL heteromeric complex. In cultured cells, overexpressed ALS2CL is colocalized with ALS2 onto membranous compartments. Further, ALS2CL dominantly suppresses the endosome enlargement induced by a constitutively active form of ALS2, and results in an extensive perinuclear tubulo-membranous phenotype, which are dependent upon the ALS2CL–ALS2 interaction. Collectively, ALS2CL is a novel ALS2-interacting protein and is implicated in ALS2-mediated endosome dynamics.