| Here we examine the function of MICAL-2, a member of a family of recently described atypical actin regulatory proteins. MICAL-2 is homologous to MICAL-1, which binds to F-actin and triggers its depolymerization by inducing methionine S-oxidation. We show that MICAL-2 is enriched in the nucleus, and induces depolymerization of nuclear F-actin. Expression of MICAL-2 leads to depletion of nuclear actin, resulting in nuclear retention of MRTF-A, and subsequent activation of SRF/MRTF-A gene transcription. MICAL-2 expression leads to morphological changes consistent with increased SRF/MRTF-A activity. Furthermore, we find that MICAL-2 is required for growth factor-induced activation of SRF/MRTF-A gene transcription. These effects of MICAL-2 occur independently of RhoA, identifying MICAL-2 as a regulator of nuclear actin and a mediator of growth factor-dependent SRF/MRTF-A signaling. |
