Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood.
Mutations in the ALS2 gene, which encodes alsin, cause autosomal recessive juvenile-onset amyotrophic lateral sclerosis (ALS2) and related conditions. Using both a novel monoclonal antibody and LacZ knock-in mice, we demonstrate that alsin is widely expressed in neurons of the CNS, including the cortex, brain stem and motor neurons of the spinal cord. Interestingly, the highest levels of alsin are found in the molecular layer of the cerebellum, a brain region not previously implicated in ALS2. During development, alsin is expressed by day E9.5, but CNS expression does not become predominant until early postnatal life. At the subcellular level, alsin is tightly associated with endosomal membranes and is likely to be part of a large protein complex that may include the actin cytoskeleton. ALS2 is present in primates, rodents, fish and flies, but not in the nematode worm or yeast, and is more highly conserved than expected among mammals. Additionally, the product of a second, widely expressed gene, ALS2 C-terminal like (ALS2CL), may subserve or modulate some of the functions of alsin as an activator of Rab and Rho GTPases.
Devon
Rebecca S
RS
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children and Women's Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
Schwab
Claudia
C
Topp
Justin D
JD
Orban
Paul C
PC
Yang
Yu-Zhou
YZ
Pape
Terry D
TD
Helm
Jeffrey R
JR
Davidson
Tara-Lynne
TL
Rogers
Daniel A
DA
Gros-Louis
Francois
F
Rouleau
Guy
G
Horazdovsky
Bruce F
BF
Leavitt
Blair R
BR
Hayden
Michael R
MR
D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000852:Anopheles; D002352:Carrier Proteins / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D002525:Cerebellar Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D004331:Drosophila melanogaster; D011992:Endosomes / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D002679:Pan troglodytes; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D023741:Takifugu; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
C438187:ALS2 protein, human; C493234:ALS2CL protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D029961:Zebrafish Proteins; C531906:als2a protein, zebrafish