Anti-CAMSAP2 monoclonal antibody, clone FQS8829(C)

Polarized, non-overlapping, regularly spaced, tiled organization of radial glial cells (RGCs) serves as a framework to generate and organize cortical neuronal columns, layers, and circuitry. Here, we show that mediator of cell motility 1 (Memo1) is a critical determinant of radial glial tiling during neocortical development. Memo 1 deletion or knockdown leads to hyperbranching of RGC basal processes and disrupted RGC tiling, resulting in aberrant radial unit assembly and neuronal layering. Memo1 regulates microtubule (MT) stability necessary for RGC tiling. Memo1 deficiency leads to disrupted MT minus-end CAMSAP2 distribution, initiation of aberrant MT branching, and altered polarized trafficking of key basal domain proteins such as GPR56, and thus aberrant RGC tiling. These findings identify Memo1 as a mediator of RGC scaffold tiling, necessary to generate and organize neurons into functional ensembles in the developing cerebral cortex.

Microtubules are cytoskeletal polymers with two structurally and functionally distinct ends, the plus- and the minus-end. Here, we focus on the mechanisms underlying the regulation of microtubule minus-ends by the CAMSAP/Nezha/Patronin protein family. We show that CAMSAP2 is required for the proper organization and stabilization of interphase microtubules and directional cell migration. By combining live-cell imaging and in vitro reconstitution of microtubule assembly from purified components with laser microsurgery, we demonstrate that CAMSAPs regulate microtubule minus-end growth and are specifically deposited on the lattice formed by microtubule minus-end polymerization. This process leads to the formation of CAMSAP-decorated microtubule stretches, which are stabilized from both ends and serve as sites of noncentrosomal microtubule outgrowth. The length of the stretches is regulated by the microtubule-severing protein katanin, which interacts with CAMSAPs. Our data thus indicate that microtubule minus-end assembly drives the stabilization of noncentrosomal microtubules and that katanin regulates this process.