Endodomain diversity in the Drosophila Dscam and its roles in neuronal morphogenesis.
Drosophila Down syndrome cell adhesion molecule (Dscam) can be variably spliced to encode 152,064 distinct single-pass transmembrane proteins. In addition to 19,008 possible ectodomains and two alternative transmembrane segments, it may carry endodomains containing or lacking exons 19 and 23. Here, we determine the role of Dscam endodomain diversity in neural development. Dscam with full-length endodomain is largely restricted to embryogenesis. In contrast, most Dscams lack exons 19 and 23 at postembryonic stages. As implicated from the expression patterns, removal of Dscam exon 19-containing variants disrupts wiring of embryonic neurons while silencing of Dscam transcripts lacking exon 19 or exon 23 effectively blocks postembryonic neuronal morphogenesis. Furthermore, compared with exon 19-containing Dscam, transgenic Dscam without exon 19 is more efficiently targeted to neurites and more potently suppresses axon bifurcation in Dscam mutant neurons. In sum, Dscam with or without exon 19 in its endodomain is used to govern different stage-specific neuronal morphogenetic processes, possibly due to differences in protein targeting.
Yu
Hung-Hsiang
HH
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Yang
Jacob S
JS
Wang
Jian
J
Huang
Yaling
Y
Lee
Tzumin
T
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015815:Cell Adhesion Molecules; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila