ALS2CL, the novel protein highly homologous to the carboxy-terminal half of ALS2, binds to Rab5 and modulates endosome dynamics.
ALS2, the causative gene product for juvenile recessive amyotrophic lateral sclerosis (ALS2), is a guanine-nucleotide exchange factor for the small GTPase Rab5. Here, we report a novel ALS2 homologous gene, ALS2 C-terminal like (ALS2CL), which encodes a 108-kD ALS2CL protein. ALS2CL exhibited a specific but a relatively weak Rab5-GEF activity with accompanying rather strong Rab5-binding properties. In HeLa cells, co-expression of ALS2CL and Rab5A resulted in a unique tubulation phenotype of endosome compartments with significant colocalization of ALS2CL and Rab5A. These results suggest that ALS2CL is a novel factor modulating the Rab5-mediated endosome dynamics in the cells.
Hadano
Shinji
S
Department of Molecular Neuroscience, The Institute of Medical Sciences, Tokai University, Isehara, Kanagawa 259-1193, Japan.
Otomo
Asako
A
Suzuki-Utsunomiya
Kyoko
K
Kunita
Ryota
R
Yanagisawa
Yoshiko
Y
Showguchi-Miyata
Junko
J
Mizumura
Hikaru
H
Ikeda
Joh-E
JE
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C438187:ALS2 protein, human; C493234:ALS2CL protein, human; C493235:ALS2CL protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D020696:rab5 GTP-Binding Proteins