Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in mouse pancreatic β cells.

Abstract

In pancreatic islet β cells, molecular motors use cytoskeletal polymers microtubules as tracks for intracellular transport of insulin secretory granules. The β-cell microtubule network has a complex architecture and is nondirectional, which provides insulin granules at the cell periphery for rapid secretion response, yet to avoid oversecretion and subsequent hypoglycemia. We have previously characterized a peripheral sub-membrane microtubule array, which is critical for the withdrawal of excessive insulin granules from the secretion sites. Microtubules in β cells originate at the Golgi in the cell interior, and how the peripheral array is formed remains unknown. Here, we demonstrate that kinesin KIF5B, a motor protein with the capacity to transport microtubules as cargos, is needed to align sub-membrane microtubules in clonal mouse β cells MIN6 and β cells within intact mouse islets. Real-time imaging and photokinetics approaches indicate that KIF5B actively slides existing microtubules to the β-cell periphery. Moreover, like many physiological β-cell features, microtubule sliding is facilitated by a high glucose stimulus. These new data, together with our previous report that high glucose destabilizes the sub-membrane microtubule array to allow for robust secretion, indicate that MT sliding is another integral part of glucose-triggered microtubule remodeling, likely replacing destabilized peripheral microtubules to prevent their loss over time and β-cell malfunction.