F-actin determines the time-dependent shift in docking dynamics of glucagon-like peptide-1 granules upon stimulation of secretion

Although exocytosis can be categorized into several forms based on docking dynamics, temporal regulatory mechanisms of the exocytotic forms are unclear. We explored the dynamics of glucagon-like peptide-1 (GLP-1) exocytosis in murine GLUTag cells (GLP-1-secreting enteroendocrine L-cells) upon stimulation with deoxycholic acid (DCA) or high K+ to elucidate the mechanisms regulating the balance between the different types of exocytotic forms (pre-docked with the plasma membrane before stimulation; docked after stimulation and subsequently fused; or rapidly recruited and fused after stimulation, without stable docking). GLP-1 exocytosis showed a biphasic pattern, and we found that most exocytosis was from the pre-docked granules with the plasma membrane before stimulation, or granules rapidly fused to the plasma membrane without docking after stimulation. In contrast, granules docked with the plasma membrane after stimuli and eventually fused were predominant thereafter. Inhibition of actin polymerization suppressed exocytosis of the pre-docked granules. These results suggest that the docking dynamics of GLP-1 granules shows a time-dependent biphasic shift, which is determined by interaction with F-actin.

Automated summary

We investigated the dynamics of GLP-1 exocytosis and found that it displayed a biphasic pattern, with most exocytosis occurring from pre-docked granules or rapidly fused granules without stable docking. Granules that docked with the plasma membrane after stimulation and subsequently fused were predominant. Inhibition of actin polymerization suppressed exocytosis of pre-docked granules. These results suggest that the docking dynamics of GLP-1 granules show a time-dependent biphasic shift, which is determined by interaction with F-actin.