Differential regulation of actin microfilaments by human MICAL proteins

Sai Srinivas Panapakkam Giridharan, Jennifer L. Rohn, Naava Naslavsky, Steven H Caplan

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)614-624
Number of pages11
JournalJournal of cell science
Volume125
Issue number3
DOIs
StatePublished - Feb 1 2012

Fingerprint

Actin Cytoskeleton
Actins
Stress Fibers
Semaphorins
Drosophila Proteins
Growth Cones
Myofibrils
Drosophila
Reactive Oxygen Species
Protein Isoforms
Proteins
human MICAL1 protein
plexin

Keywords

  • Actin
  • Actin-rich protrusions
  • MICAL1
  • MICAL2
  • Microfilaments
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cell Biology

Cite this

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

In: Journal of cell science, Vol. 125, No. 3, 01.02.2012, p. 614-624.

Research output: Contribution to journalArticle

Giridharan, Sai Srinivas Panapakkam ; Rohn, Jennifer L. ; Naslavsky, Naava ; Caplan, Steven H. / Differential regulation of actin microfilaments by human MICAL proteins. In: Journal of cell science. 2012 ; Vol. 125, No. 3. pp. 614-624.
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