doublecortin, a Brain-Specific Gene Mutated in Human X-Linked Lissencephaly and Double Cortex Syndrome, Encodes a Putative Signaling Protein

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• 作者：Joseph G. Gleeson ; Kristina M. Allen ; Jeremy W. Fox ; Edward D. Lamperti ; Samuel Berkovic ; Ingrid Scheffer ; Edward C. Cooper ; William B. Dobyns ; Sharon R. Minnerath ; M. Elizabeth Ross ; Christopher A. Walsh
• 刊名：Cell
• 出版年：1998
• 出版时间：9 January 1998
• 年：1998
• 卷：92
• 期：1
• 页码：63-72
• 全文大小：2276 K

文摘

X-linked lissencephaly and “double cortex” are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin. Four double cortex/X-linked lissencephaly families and three sporadic double cortex patients show independent doublecortin mutations, at least one of them a de novo mutation. Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin does not contain a kinase domain, it is homologous to the amino terminus of a predicted kinase protein, indicating a likely role in signal transduction. Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration.