MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion

Jonathan R. Terman, Tianyi Mao, R. Jeroen Pasterkamp, Hung Hsiang Yu, Alex L. Kolodkin

Research output: Contribution to journalArticle

254 Scopus citations

Abstract

Members of the semaphorin family of secreted and transmembrane proteins utilize plexins as neuronal receptors to signal repulsive axon guidance. It remains unknown how plexin proteins are directly linked to the regulation of cytoskeletal dynamics. Here, we show that Drosophila MICAL, a large, multidomain, cytosolic protein expressed in axons, interacts with the neuronal plexin A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. In addition to containing several domains known to interact with cytoskeletal components, MICAL has a flavoprotein monooxygenase domain, the integrity of which is required for Sema-1a-PlexA repulsive axon guidance. Vertebrate orthologs of Drosophila MICAL are neuronally expressed and also interact with vertebrate plexins, and monooxygenase inhibitors abrogate semaphorin-mediated axonal repulsion. These results suggest a novel role for oxidoreductases in repulsive neuronal guidance.

Original languageEnglish (US)
Pages (from-to)887-900
Number of pages14
JournalCell
Volume109
Issue number7
DOIs
StatePublished - Jun 28 2002

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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