Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding

被引:254
作者
Wojtowicz, WM [1 ]
Flanagan, JJ [1 ]
Millard, SS [1 ]
Zipursky, SL [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Howard Hughes Med Inst, Los Angeles, CA 90095 USA
关键词
D O I
10.1016/j.cell.2004.08.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dscam is an immunoglobulin (Ig) superfamily protein required for the formation of neuronal connections in Drosophila. Through alternative splicing, Dscam potentially gives rise to 19,008 different extracellular domains linked to one of two alternative transmembrane segments, resulting in 38,016 isoforms. All isoforms share the same domain structure but contain variable amino acid sequences within three Ig domains in the extracellular region. We demonstrate that different isoforms exhibit different binding specificity. Each isoform binds to itself but does not bind or binds poorly to other isoforms. The amino acid sequences of all three variable Ig domains determine binding specificity. Even closely related isoforms sharing nearly identical amino acid sequences exhibit isoform-specific binding. We propose that this preferential homophilic binding specificity regulates interactions between cells and contributes to the formation of complex patterns of neuronal connections.
引用
收藏
页码:619 / 633
页数:15
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