Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell adhesion molecule that mediates homophilic intercellular adhesion.
DSCAM, a conserved gene involved in neuronal differentiation, is a member of the Ig superfamily of cell adhesion molecules. Herein, we report the functional characterization of a human DSCAM (Down syndrome cell adhesion molecule) paralogue, DSCAML1, located on chromosome 11q23. The deduced DSCAML1 protein contains 10 Ig domains, six fibronectin-III domains, and an intracellular domain, all of which are structurally identical to DSCAM. When compared to DSCAM, DSCAML1 protein showed 64% identity to the extracellular domain and 45% identity to the cytoplasmic domain. In the mouse brain, DSCAML1 is predominantly expressed in Purkinje cells of the cerebellum, granule cells of the dentate gyrus, and in neurons of the cerebral cortex and olfactory bulb. Biochemical and immunofluorescence analyses indicated that DSCAML1 is a cell surface molecule that targets axonal features in differentiated PC12 cells. DSCAML1 exhibits homophilic binding activity that does not require divalent cations. Based on its structural and functional properties and similarities to DSCAM, we suggest that DSCAML1 may be involved in formation and maintenance of neural networks. The chromosomal locus for DSCAML1 makes it an ideal candidate for neuronal disorders (such as Gilles de la Tourette and Jacobsen syndromes) that have been mapped on 11q23.
Agarwala
K L
KL
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, 2-1 Hirosawa, Saitama 351-0198, Japan.
Ganesh
S
S
Tsutsumi
Y
Y
Suzuki
T
T
Amano
K
K
Yamakawa
K
K
D000818:Animals; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004330:Drosophila; D029721:Drosophila Proteins; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; C110833:DSCAM protein, human; C432365:DSCAML1 protein, human; C486620:DSCAML1 protein, mouse; D029721:Drosophila Proteins; C491735:Dscam protein, mouse; C491736:Dscam1 protein, Drosophila; D008565:Membrane Proteins; D011506:Proteins