Abstract
Glucose stimulation induces the remodeling of microtubules, which potentiates insulin secretion in pancreatic β-cells. CAMSAP2 binds to microtubule minus ends to stabilize microtubules in several cultured clonal cells. Here, we report that the knockdown of CAMSAP2 in primary β-cells reduces total insulin content and attenuates GSIS without affecting the releasability of insulin vesicles. Surprisingly, CAMSAP2 knockdown does not change microtubule stability. Unlike in cultured insulinoma cells, CAMSAP2 in primary β-cells predominantly localizes to the Golgi apparatus instead of microtubule minus ends. This novel localization is specific to primary β- but not α-cells and is independent of microtubule binding. Consistent with its specific localization at the Golgi, CAMSAP2 promotes efficient Golgi-ER trafficking in primary β-cells. Moreover, primary β-cells and insulinoma cells likely express different CAMSAP2 isoforms. We propose that a novel CAMSAP2 isoform in primary β-cells has a non-canonical function, which promotes Golgi-ER trafficking to support efficient production of insulin and secretion.