title: Human down syndrome cell adhesion molecules (DSCAMs) are functionally conserved with Drosophila Dscam[TM1] isoforms in controlling neurodevelopment.
abstract: Drosophila Down syndrome cell adhesion molecule (Dscam) potentially produces more than 150,000 cell adhesion molecules that share two alternative transmembrane/juxtamembrane (TM) domains, which dictate the dendrite versus axon subcellular distribution and function of different Dscam isoforms. Vertebrate genomes contain two closely related genes, DSCAM and DSCAM-Like1 (DSCAML1), which do not have extensive alternative splicing. We investigated the functional conservation between invertebrate Dscams and vertebrate DSCAMs by cross-species rescue assays and found that human DSCAM and DSCAML1 partially, but substantially, rescued the larval lethality of Drosophila Dscam mutants. Interestingly, both human DSCAM and DSCAML1 were targeted to the dendrites in Drosophila neurons, had synergistic rescue effects with Drosophila Dscam[TM2], and preferentially rescued the dendrite defects of Drosophila Dscam mutant neurons. Therefore, human DSCAM and DSCAML1 are functionally conserved with Drosophila Dscam[TM1] isoforms.
authors.affiliation: Department of Entomology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Raghavan
authors.forename: Siqian
authors.initials: S
authors.lastname: Feng
authors.forename: Kurtis
authors.initials: K
authors.lastname: Kiesewetter
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D006801:Humans; D007814:Larva / Q000502:physiology; D009154:Mutation; D009420:Nervous System / Q000254:growth & development; D010802:Phylogeny; D020033:Protein Isoforms; D040681:Structural Homology, Protein
chemical_list: D015815:Cell Adhesion Molecules; C110833:DSCAM protein, human; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D020033:Protein Isoforms