Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope

Abstract

Non-centrosomal microtubule organizing centers (ncMTOC) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in myoblasts for recruiting centrosomal proteins. Moreover, myogenin is sufficient in fibroblasts for ncMTOC formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated ncMTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and ncMTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the ncMTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous centrosomal proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an ncMTOC and identify AKAP6 as a novel ncMTOC component in muscle cells.