MICAL flavoprotein monooxygenases: expression during neural development and following spinal cord injuries in the rat.
MICALs comprise of a family of phylogenetically conserved, multidomain cytosolic flavoprotein monooxygenases. Drosophila (D-)MICAL binds the neuronal Sema1a receptor PlexA, and D-MICAL-PlexA interactions are required in vivo for Sema1a-induced axon repulsion. The biological functions of vertebrate MICAL proteins, however, remain unknown. Here, we describe three rodent MICAL genes and analyze their expression in the intact rat nervous system and in two models of spinal cord injury. MICAL-1, -2, and -3 expression patterns in the embryonic, postnatal, and adult nervous system support the idea that MICALs play roles in neural development and plasticity. In addition, MICAL expression is elevated in oligodendrocytes and in meningeal fibroblasts at sites of spinal cord injury but is unchanged in lesioned corticospinal tract neurons. Furthermore, we find that the selective monooxygenase inhibitor EGCG attenuates the repulsive effects of Sema3A and Sema3F in vitro, but not those of several other repulsive cues and substrates. These results implicate MICALs in neuronal regeneration and support the possibility of employing EGCG to attenuate Sema3-mediated axon repulsion in the injured spinal cord.
Pasterkamp
R Jeroen
RJ
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. j.pasterkamp@med.uu.nl
Dai
Hai-ning
HN
Terman
Jonathan R
JR
Wahlin
Karl J
KJ
Kim
Byung
B
Bregman
Barbara S
BS
Popovich
Phillip G
PG
Kolodkin
Alex L
AL
D000818:Animals; D001921:Brain / Q000254:growth & development; D004195:Disease Models, Animal; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000503:physiopathology*
D005420:Flavoproteins; D008869:Microtubule-Associated Proteins; D006899:Mixed Function Oxygenases