RESEARCH: Info on Alsin

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This abstract mentions only ALS. But defective Alsin

can also cause juvenile onset PLS.

Alsin is a Rab5 and Rac1 guanine nucleotide exchange

factor.

Topp JD, Gray NW, Gerard RD, Horazdovsky BF.

Biochemistry and Molecular Biology, Mayo Clinic,

Rochester, MN 55905.

ALS2 is the gene mutated in a recessive juvenile form

of amyotrophic lateral sclerosis (ALS2). ALS2 encodes

a large protein termed Alsin, which contains a number

of predicted cell signaling and protein trafficking

sequence motifs. To gain insight into the overall

function of Alsin and to begin to evaluate its role in

motor neuron maintenance, we examined the subcellular

localization of Alsin and the biochemical activities

associated with its individual subdomains. We show

that the Vps9p domain of Alsin has Rab5 guanine

nucleotide exchange activity. In addition, Alsin

interacted specifically with and acted as a guanine

nucleotide exchange factor for Rac1.

Immunofluorescence and fractionation experiments in

both fibroblasts and neurons revealed that Alsin is a

cytosolic protein, with a significant portion

associated with small, punctate membrane structures.

Many of these membrane structures also contained Rab5

or Rac1. Finally, we found that Alsin was present in

membrane ruffles and lamellipodia. These data suggests

that Alsin is involved in membrane transport events,

potentially linking endocytic processes and actin

cytoskeleton remodeling.

SOURCE: J Biol Chem. 2004 Mar 19 [Epub ahead of

print]

http://www.jbc.org/cgi/reprint/M313504200v1