title: Differential regulation of actin microfilaments by human MICAL proteins.
abstract: The Drosophila melanogaster MICAL protein is essential for the neuronal growth cone machinery that functions through plexin- and semaphorin-mediated axonal signaling. Drosophila MICAL is also involved in regulating myofilament organization and synaptic structures, and serves as an actin disassembly factor downstream of plexin-mediated axonal repulsion. In mammalian cells there are three known isoforms, MICAL1, MICAL2 and MICAL3, as well as the MICAL-like proteins MICAL-L1 and MICAL-L2, but little is known of their function, and information comes almost exclusively from neural cells. In this study we show that in non-neural cells human MICALs are required for normal actin organization, and all three MICALs regulate actin stress fibers. Moreover, we provide evidence that the generation of reactive oxygen species by MICAL proteins is crucial for their actin-regulatory function. However, although MICAL1 is auto-inhibited by its C-terminal coiled-coil region, MICAL2 remains constitutively active and affects stress fibers. These data suggest differential but complementary roles for MICAL1 and MICAL2 in actin microfilament regulation.
authors.affiliation: Department of Biochemistry and Molecular Biology and Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870,  USA.
authors.forename: Sai Srinivas Panapakkam
authors.initials: SS
authors.lastname: Giridharan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rohn
authors.forename: Naava
authors.initials: N
authors.lastname: Naslavsky
authors.forename: Steve
authors.initials: S
authors.lastname: Caplan
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006899:Mixed Function Oxygenases; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism; D015398:Signal Transduction; D000096985:Calponins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D009419:Nerve Tissue Proteins; D010088:Oxidoreductases; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D039961:Semaphorins; C496247:MICAL protein, Drosophila; C528177:MICALL2 protein, human; C091529:plexin; C455272:MICAL1 protein, human; D000096985:Calponins; C587931:MICAL2 protein, human