TY - JOUR
T1 - MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion
AU - Terman, Jonathan R.
AU - Mao, Tianyi
AU - Pasterkamp, R. Jeroen
AU - Yu, Hung Hsiang
AU - Kolodkin, Alex L.
N1 - Funding Information:
We especially thank Y.-C. Wu for Drosophila technical assistance, N. Schumann and S. Kohli for help with yeast interaction assays, and C. Foster for help with MICAL-FM purification and analysis. We thank A. Ghosh, D. Ginty, and H. Sink for helpful comments on the manuscript, and M. Amzel, K. Cook, C. Foster, M. Grimes, and members of the Kolodkin and Ginty laboratories for helpful discussions. We thank M. Ashburner, H. Araj, C. Goodman, H. Fujisawa, T. Nagase, J. Roote, L. Tamagnone, D. VanVactor, K. Zinn, the Bloomington Stock Center, and the Berkeley Drosophila Genome Project for cDNA libraries, fly stocks, antibodies, and cDNAs. Supported by National Institutes of Health (NRSA-NS11055) and The Paralyzed Veterans Association of America/Spinal Cord Research Foundation (#2050) (J.R.T), the Netherlands Organization for Scientific Research and Human Frontier Science Organization (R.J.P.), and NIH grant NS35165 (A.L.K.).
PY - 2002/6/28
Y1 - 2002/6/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037188897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037188897&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(02)00794-8
DO - 10.1016/S0092-8674(02)00794-8
M3 - Article
C2 - 12110185
AN - SCOPUS:0037188897
SN - 0092-8674
VL - 109
SP - 887
EP - 900
JO - Cell
JF - Cell
IS - 7
ER -