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

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, multid...

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Veröffentlicht in:Cell 2002-06, Vol.109 (7), p.887-900
Hauptverfasser: Terman, Jonathan R., Mao, Tianyi, Pasterkamp, R.Jeroen, Yu, Hung-Hsiang, Kolodkin, Alex L.
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container_end_page 900
container_issue 7
container_start_page 887
container_title Cell
container_volume 109
creator Terman, Jonathan R.
Mao, Tianyi
Pasterkamp, R.Jeroen
Yu, Hung-Hsiang
Kolodkin, Alex L.
description 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.
doi_str_mv 10.1016/S0092-8674(02)00794-8
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subjects Actins - metabolism
Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
Axons - enzymology
Axons - metabolism
Binding Sites
Blotting, Western
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules, Neuronal - genetics
Cell Adhesion Molecules, Neuronal - metabolism
Conserved Sequence
Cytoskeletal Proteins - antagonists & inhibitors
Cytoskeletal Proteins - chemistry
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
Cytoskeleton - metabolism
Drosophila melanogaster - enzymology
Drosophila melanogaster - genetics
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Flavin-Adenine Dinucleotide - metabolism
Flavoproteins - antagonists & inhibitors
Flavoproteins - chemistry
Flavoproteins - genetics
Flavoproteins - metabolism
Humans
Intracellular Signaling Peptides and Proteins
LIM Domain Proteins
Molecular Sequence Data
Mutation
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Oxidoreductases - antagonists & inhibitors
Oxidoreductases - chemistry
Oxidoreductases - genetics
Oxidoreductases - metabolism
Phenotype
Protein Binding
Protein Structure, Tertiary
Semaphorins
Sequence Homology, Amino Acid
Signal Transduction
title MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion
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