Neurexin-1α Contributes to Insulin-containing Secretory Granule Docking

Abstract

Background:The cell surface, transmembrane protein neurexin may play a role in insulin secretion. Results: Knockdown and knock-out of neurexin-1␣, the predominant ␤-cell isoform, increased insulin secretion and impaired secretory granule docking. Conclusion: Neurexin-1␣ helps mediate insulin granule docking and thereby constrains secretion. Significance: Neurexin-1␣ could couple localization and functioning of the insulin docking and secretory machinery to extracellular protein interactions.

Filtration is a time-efficient option to Histopaque, providing good-quality islets in mouse islet isolation

“…Therefore, we decided to filter preparations through a 100 lm cell strainer, as reported by Salvalaggio et al (2002). Other reports included an extra step of purification by handpicking after applying this protocol (Daniel et al 2011;Dhanesha et al 2012;Mosedale et al 2012;Pang et al 2010) and our results further confirm the improvement of islet purity after adding this extra step.…”

Transcellular Neuroligin-2 Interactions Enhance Insulin Secretion and Are Integral to Pancreatic β Cell Function

“…Neuroligin-1 (NL-1) can similarly increase insulin secretion. Although neurexin-1␣, a major neuroligin binding partner, is present on the ␤ cell surface, neurexin binding is not necessary in order for neuroligin to influence insulin secretion (16). In longer term experiments, transcellular NL-2 interactions increased INS-1 ␤ cell proliferation and insulin content.…”

“…The proteins with which neuroligins interact to mediate their neurexin-independent functions are as yet unknown (36). Because ␤ cells express neurexin, primarily neurexin-1␣, we next asked if neurexin binding is necessary for neuroligin to cause increased insulin secretion (14,16). Small, discrete mutations preventing the interaction of NL-2 with neurexins have not been described.…”

“…Neurexins, which are known neuroligin binding partners, are also expressed by ␤ cells (14,16). To test for NL-2 binding to the ␤ cell surface, flow cytometry was performed after incubating INS-1 ␤ cells with the extracellular domain of NL-2 (soluble NL-2).…”

Protein sorting gone wrong – VPS10P domain receptors in cardiovascular and metabolic diseases

“…Thus, in neurons, SORCS1 interacts with the synaptic adhesion molecule neurexin and controls trafficking of glutamate receptors, a process critical for plasticity of the synapse 59 . Remarkably, neurexin-1α and its ligand neuroligin are also expressed in pancreatic β-cells where they interact with components of the SG docking machinery to modulate insulin secretion rates [60][61][62] . Consequently, loss of expression of neurexin-1α 62 or neuroligin-2 63 alters islet morphology, pancreatic insulin content, and insulin secretion in mice.…”