Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.

Rab26 is known to regulate multiple membrane trafficking events, but its role in insulin secretion in pancreatic ß cells remains unclear despite it was first identified in the pancreas. In this study, we generated Rab26-/- mice through CRISPR/Cas9 technique. Surprisingly, insulin levels in the blood of the Rab26-/- mice do not decrease upon glucose stimulation but conversely increase. Deficiency of Rab26 promotes insulin secretion, which was independently verified by Rab26 knockdown in pancreatic insulinoma cells. Conversely, overexpression of Rab26 suppresses insulin secretion in both insulinoma cell lines and isolated mouse islets. Islets overexpressing Rab26, upon transplantation, also failed to restore glucose homeostasis in type 1 diabetic mice. Immunofluorescence microscopy revealed that overexpression of Rab26 results in clustering of insulin granules. GST-pulldown experiments reveal that Rab26 interacts with synaptotagmin-1 (Syt1) through directly binding to its C2A domain, which interfering with the interaction between Syt1 and SNAP25, and consequently inhibiting the exocytosis of newcomer insulin granules revealed by TIRF microscopy. Our results suggest that Rab26 serves as a negative regulator of insulin secretion, via suppressing insulin granule fusion with plasma membrane through sequestering Syt1.

Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src.

Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.

Bioactive Pore-Forming Bone Adhesives Facilitating Cell Ingrowth for Fracture Healing.

The effectiveness of commercial bone adhesives is known to be hampered by the weak efficacy of cell ingrowth. The strategy of macropore-forming, especially bioactive macropores, holds considerable promise to circumvent this problem, thereby promoting fracture healing. Herein, a class of bioactive glass-involved macropore-embedded bone adhesives is developed, which is capable of facilitating the migration of bone-derived mesenchymal stromal cells into the adhesive layer and differentiation into osteocytes. The integration of bioactive glass-particle-encapsulated porogens in the bone adhesives is key to this approach. A robust instant bonding on the bone adhesive and a high efficiency of bone regeneration on a mouse skull are observed, both of which are vital for clinical applications and personalized surgical procedures. This work represents a general strategy to design biomaterials with high cell-ingrowth efficacy.