Myocardin-related transcription factor and serum response factor regulate cilium turnover by both transcriptional and local mechanisms
Pam Speight,
Matthew Rozycki,
Shruthi Venugopal,
Katalin Szászi,
Michael Kofler,
András Kapus
Affiliations
Pam Speight
Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada
Matthew Rozycki
Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada
Shruthi Venugopal
Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada
Katalin Szászi
Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada; Department of Surgery, University of Toronto, Toronto, ON M5B 1T8, Canada
Michael Kofler
Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada
András Kapus
Keenan Research Centre for Biomedical Science of the St. Michael's Hospital, University of Toronto, Room 621, 209 Victoria Street, Toronto, ON M5B 1T8, Canada; Department of Surgery, University of Toronto, Toronto, ON M5B 1T8, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5B 1T8, Canada; Corresponding author
Summary: Turnover of the primary cilium (PC) is critical for proliferation and tissue homeostasis. Each key component of the PC resorption machinery, the HEF1/Aurora kinase A (AurA)/HDAC6 pathway harbors cis-elements potentially targeted by the transcriptional co-activator myocardin-related transcription factor (MRTF) and/or its partner serum response factor (SRF). Thus we investigated if MRTF and/or SRF regulate PC turnover. Here we show that (1) both MRTF and SRF are indispensable for serum-induced PC resorption, and (2) they act via both transcriptional and local mechanisms. Intriguingly, MRTF and SRF are present in the basal body and/or the PC, and serum facilitates ciliary MRTF recruitment. MRTF promotes the stability and ciliary accumulation of AurA and facilitates SRF phosphorylation. Ciliary SRF interacts with AurA and HDAC6. MRTF also inhibits ciliogenesis. It 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.
