Spatial relief of Kinesin-1 auto-inhibition by Ensconsin regulates ncMTOCs localization and shapes microtubule networks

Abstract

During Drosophila oogenesis, the organization of microtubules (MTs) drives polarized transport and cytoplasmic flows. Although Kinesin-1 plays a central role in these processes, its molecular and spatial regulation remains poorly understood. Here, we show that Ensconsin, an activator of the Kinesin heavy chain (Khc), is enriched in the oocyte through MT binding, Dynein-mediated transport and by the MT-anchoring protein Ninein. Strikingly, loss of Ensconsin enrichment reduces cortical non-centrosomal microtubule-organizing centers (ncMTOCs), weakens MT nucleation, impairs MT organization and MT-dependent cytoplasmic flows. Additionally, a specific Khc variant unable to bind Ensconsin, is constitutively active and is able to partly rescue the loss of Ensconsin in oocyte and neural stem cells, thereby providing in vivo support for the relief-of-auto-inhibition model. Overall, we uncover a novel function for the Khc-Ensconsin complex in the recruitment of ncMTOCs in oocytes for MT organization. Our findings are in line with a model in which Ensconsin enrichment acts as a rheostat to modulate Khc activation, ensuring precise spatial remodeling of the microtubule cytoskeleton in the oocyte.

The authors' abstract, as published at the source. Journal of Cell Science, 2026 · DOI ↗