| First Author | Ma W | Year | 2020 |
| Journal | J Cell Sci | Volume | 133 |
| Issue | 6 | PubMed ID | 32079655 |
| Mgi Jnum | J:288882 | Mgi Id | MGI:6416577 |
| Doi | 10.1242/jcs.236794 | Citation | Ma W, et al. (2020) Arp2/3 nucleates F-actin coating of fusing insulin granules in pancreatic beta cells to control insulin secretion. J Cell Sci 133(6):jcs236794 |
| abstractText | F-actin dynamics are known to control insulin secretion, but the point of intersection with the stimulus-secretion cascade is unknown. Here, using multiphoton imaging of beta cells isolated from Lifeact-GFP transgenic mice, we show that glucose stimulation does not cause global changes in subcortical F-actin. Instead, we observe spatially discrete and transient F-actin changes around each fusing granule. This F-actin remodelling is dependent on actin nucleation and is observed for granule fusion induced by either glucose or high potassium stimulation. Using GFP-labelled proteins, we identify local enrichment of Arp3, dynamin 2 and clathrin, all occurring after granule fusion, suggesting early recruitment of an endocytic complex to the fusing granules. Block of Arp2/3 activity with drugs or shRNA inhibits F-actin coating, traps granules at the cell membrane and reduces insulin secretion. Block of formin-mediated actin nucleation also blocks F-actin coating, but has no effect on insulin secretion. We conclude that local Arp2/3-dependent actin nucleation at the sites of granule fusion plays an important role in post-fusion granule dynamics and in the regulation of insulin secretion. |
