ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome dynamics.
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.
Suzuki-Utsunomiya
Kyoko
K
Department of Molecular Neuroscience, The Institute of Medical Sciences, Tokai University, Kanagawa, Japan.
Hadano
Shinji
S
Otomo
Asako
A
Kunita
Ryota
R
Mizumura
Hikaru
H
Osuga
Hitoshi
H
Ikeda
Joh-E
JE
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
C438187:ALS2 protein, human; C493234:ALS2CL protein, human; D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors