The centrosomal recruitment of γ-tubulin and its microtubule nucleation activity is α-fodrin guided

The regulation and recruitment of gamma-TuRCs, the prime nucleator of microtubules, to the centrosome are still thrust areas of research. The interaction of fodrin, a sub-plasmalemmal cytoskeletal protein, with gamma-tubulin is a new area of interest. To understand the cellular significance of this interaction, we show that depletion of alpha-fodrin brings in a significant reduction of gamma-tubulin in neural cell centrosomes making it functionally under-efficient. This causes a loss of nucleation ability that cannot efficiently form microtubules in interphase cells and astral microtubules in mitosis. Fluorescence Recovery after Photobleaching (FRAP) experiment implies that alpha-fodrin is important in the recruitment of gamma-tubulin to the centrosome resulting in the aforementioned effects. Further, our experiments indicate that the interaction of alpha-fodrin with certain pericentriolar matrix proteins such as Pericentrin and CDK5RAP2 are crucial for the recruitment of gamma-tubulin to the centrosome. Earlier we reported that alpha-fodrin limits the nucleation potential of gamma-TuRC. In that context, this study suggests that alpha-fodrin is a gamma-tubulin recruiting protein to the centrosome thus preventing cytoplasmic microtubule nucleation and thereby compartmentalizing the process to the centrosome for maximum efficiency. Summary statement alpha-fodrin is a gamma-tubulin interacting protein that controls the process of gamma-tubulin recruitment to the centrosome and thereby regulates the microtubule nucleation capacity spatially and temporally.