title: ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome dynamics.
abstract: 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.
authors.affiliation: Department of Molecular Neuroscience, The Institute of Medical Sciences, Tokai University, Kanagawa, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki-Utsunomiya
authors.forename: Shinji
authors.initials: S
authors.lastname: Hadano
authors.forename: Asako
authors.initials: A
authors.lastname: Otomo
authors.forename: Ryota
authors.initials: R
authors.lastname: Kunita
authors.forename: Hikaru
authors.initials: H
authors.lastname: Mizumura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osuga
authors.forename: Joh-E
authors.initials: JE
authors.lastname: Ikeda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D010641:Phenotype; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C438187:ALS2 protein, human; C493234:ALS2CL protein, human; D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors