Myocardin-Related Transcription Factor and Serum Response Factor Regulate Cilium Resorption and Ciliogenesis by Both Transcriptional and Local Mechanisms

Abstract

Turnover of the primary cilium (PC) is critical for proliferation and tissue homeostasis. Since each component of the main PC resorption machinery, the HEF1/Aurora kinase A (AurA)/HDAC6 pathway harbors cis-elements (CArG boxes) potentially targeted by the transcriptional co-activator myocardin-related transcription factor (MRTF) and/or its partner serum response factor (SRF), we investigated if MRTF and/or SRF regulate PC turnover. Here we show that both MRTF and SRF are indispensable for serum-induced PC resorption, but 1) they differentially impact the expression of the members of the PC resorption machinery (e.g. HEF1); and 2) act via both transcriptional and local mechanisms. Regarding the latter mode of action, MRTF interacts with AurA and protects it from degradation. Intriguingly, both MRTF and SRF are present in the basal body and/or the PC. Serum induces MRTF recruitment to the PC, and MRTF is necessary for ciliary AurA accumulation and SRF phosphorylation. Ciliary SRF interacts with AurA and HDAC6. Finally, we show that in addition to supporting PC resorption, MRTF also inhibits ciliogenesis. MRTF interacts with and is required for the correct localization of the ciliogenesis modulator CEP290. Thus, MRTF and SRF are critical regulators of PC assembly and/or disassembly, acting both as transcription factors and as PC constituents.