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Differential regulation of actin microfilaments by human MICAL proteins
Sai Srinivas Panapakkam Giridharan, Jennifer L. Rohn, Naava Naslavsky, Steve Caplan


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.


  • Funding

    This research was supported by National Institutes of Health [grant numbers RO1GM074876, RO1GM087455 to S.C. and N.N.], the National Center for Research Resources [grant number P20 RRO18759 to N.N.], a University of Nebraska Student Assistantship Award (to S.S.P.G.) and the Welcome Trust (to J.R.). Deposited in PMC for release after 6 months.

  • Supplementary material available online at

  • Accepted September 26, 2011.
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