Vergarajauregui S, Panea S, Oltmanns JO, Steffen U, Engel F (2026)
Publication Type: Journal article
Publication year: 2026
Book Volume: 139
Journal Issue: 12
DOI: 10.1242/jcs.264166
Microtubule organization plays a central role in cell differentiation, orchestrating essential processes such as cell polarization, mechanotransduction, organelle positioning and intracellular transport. A hallmark of many differentiated cells is the transition from a centrosomal to a non-centrosomal microtubule-organizing center (MTOC). Here, we demonstrate that both centrosomal and nuclear envelope (NE)-associated MTOCs coexist in osteoclasts. We show that the key players for NE-MTOC formation, the AKAP6 and nesprin-1 (SYNE1) isoforms AKAP6β and nesprin-1α, previously considered muscle specific, are upregulated during osteoclast differentiation, suggesting a conserved role in NE-MTOC assembly across cell types. Targeted depletion of AKAP6 in RAW264.7-derived osteoclasts led to the displacement of the Golgi and MTOC-associated proteins PCM1, pericentrin and CDK5RAP2 from the NE, while their centrosomal localization remained intact. This selectively impaired microtubule nucleation from the NE without disrupting centrosomal microtubule activity, enabling a functional dissection of the two MTOCs. Loss of NE-MTOC activity, through AKAP6 depletion, impaired podosome formation and significantly reduced bone resorption capacity, highlighting the distinct and essential role of NE-derived microtubules in osteoclast function.
APA:
Vergarajauregui, S., Panea, S., Oltmanns, J.O., Steffen, U., & Engel, F. (2026). Selective disruption of microtubule formation at the nuclear envelope impairs the bone resorption capacity of osteoclasts. Journal of Cell Science, 139(12). https://doi.org/10.1242/jcs.264166
MLA:
Vergarajauregui, Silvia, et al. "Selective disruption of microtubule formation at the nuclear envelope impairs the bone resorption capacity of osteoclasts." Journal of Cell Science 139.12 (2026).
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