In pancreatic β-cells myosin 1b regulates glucose-stimulated insulin secretion by modulating an early step in insulin granule trafficking from the Golgi

• Published in: Molecular biology of the cell 2021-06, Vol.32 (12), p.1210-1220
• Main Authors: Tokuo, Hiroshi, Komaba, Shigeru, Coluccio, Lynne M
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - metabolism; Animals; Cell Line, Tumor; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - physiology; Myosin Type I - metabolism; Myosin Type I - physiology; Protein Transport; Rats; Secretory Vesicles - metabolism; trans-Golgi Network - metabolism; trans-Golgi Network - physiology
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E21-03-0094

Pancreatic β-cells secrete insulin, which controls blood glucose levels, and defects in insulin secretion are responsible for diabetes mellitus. The actin cytoskeleton and some myosins support insulin granule trafficking and release, although a role for the class I myosin Myo1b, an actin- and membrane-associated load-sensitive motor, in insulin biology is unknown. We found by immunohistochemistry that Myo1b is expressed in islet cells of the rat pancreas. In cultured rat insulinoma 832/13 cells, Myo1b localized near actin patches, the -Golgi network (TGN) marker TGN38, and insulin granules in the perinuclear region. Myo1b depletion by small interfering RNA in 832/13 cells reduced intracellular proinsulin and insulin content and glucose-stimulated insulin secretion (GSIS) and led to the accumulation of (pro)insulin secretory granules (SGs) at the TGN. Using an in situ fluorescent pulse-chase strategy to track nascent proinsulin, Myo1b depletion in insulinoma cells reduced the number of (pro)insulin-containing SGs budding from the TGN. The studies indicate for the first time that in pancreatic β-cells Myo1b controls GSIS at least in part by mediating an early stage in insulin granule trafficking from the TGN.