ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome dynamics

K Suzuki-Utsunomiya, S Hadano, A Otomo… - Biochemical and …, 2007 - Elsevier
K Suzuki-Utsunomiya, S Hadano, A Otomo, R Kunita, H Mizumura, H Osuga, JE Ikeda
Biochemical and biophysical research communications, 2007Elsevier
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 …
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.
Elsevier