TY - JOUR TI - Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope AU - Becker, Robert AU - Vergarajauregui, Silvia AU - Billing, Florian AU - Sharkova, Maria AU - Lippolis, Eleonora AU - Mamchaoui, Kamel AU - Ferrazzi, Fulvia AU - Engel, Felix B A2 - Lüders, Jens A2 - Pfeffer, Suzanne R A2 - Lüders, Jens VL - 10 PY - 2021 DA - 2021/10/04 SP - e65672 C1 - eLife 2021;10:e65672 DO - 10.7554/eLife.65672 UR - https://doi.org/10.7554/eLife.65672 AB - Non-centrosomal microtubule-organizing centers (MTOCs) 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 murine myoblasts for the localization of MTOC proteins to the nuclear envelope. Moreover, myogenin is sufficient in fibroblasts for nuclear envelope MTOC (NE-MTOC) 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 NE-MTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and NE-MTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the NE-MTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous MTOC 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 NE-MTOC and identify AKAP6 as a novel NE-MTOC component in muscle cells. KW - centrosome KW - MTOC KW - myogenin KW - microtubules KW - muscle differentiation KW - AKAP6 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -