Expression of Neurexin, Neuroligin, and Their Cytoplasmic Binding Partners in the Pancreatic β-Cells and the Involvement of Neuroligin in Insulin Secretion

Abstract

The composition of the beta-cell exocytic machinery is very similar to that of neuronal synapses, and the developmental pathway of beta-cells and neurons substantially overlap. beta-Cells secrete gamma-aminobutyric acid and express proteins that, in the brain, are specific markers of inhibitory synapses. Recently, neuronal coculture experiments have identified three families of synaptic cell-surface molecules (neurexins, neuroligins, and SynCAM) that drive synapse formation in vitro and that control the differentiation of nascent synapses into either excitatory or inhibitory fully mature nerve terminals. The inhibitory synapse-like character of the beta-cells led us to hypothesize that members of these families of synapse-inducing adhesion molecules would be expressed in beta-cells and that the pattern of expression would resemble that associated with neuronal inhibitory synaptogenesis. Here, we describe beta-cell expression of the neuroligins, neurexins, and SynCAM, and show that neuroligin expression affects insulin secretion in INS-1 beta-cells and rat islet cells. Our findings demonstrate that neuroligins and neurexins are expressed outside the central nervous system and help confer an inhibitory synaptic-like phenotype onto the beta-cell surface. Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus.

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.…”

Characterization of the neuroligin gene family expression and evolution in zebrafish

“…Previous studies have already focused on the expression pattern of Neuroligin genes in different species (from mammals to birds), but few data concerning the alternative splicing pattern variation are available (Philibert et al, 2000;Bolliger et al, 2001;Chih et al, 2006;Suckow et al, 2008).…”

“…Neuroligin 1 expression is mainly restricted to the CNS, while Neuroligins 2-4 present a broader expression pattern (Song et al, 1999;Philibert et al, 2000;Bolliger et al, 2001;Gilbert et al, 2001;Kang et al, 2004;Suckow et al, 2008). Some lines of evidence suggest that the expression of Neuroligins may differ between species.…”

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

“…We previously found that neuroligin-2 (NL-2), 3 which is specific to inhibitory (GABAergic) synapses, is expressed by pancreatic ␤ cells and that alterations in its level of expression affected insulin secretion by primary rat islet and INS-1 ␤ cells (11,14). Increased NL-2 expression caused increased insulin secretion, and decreased expression lowered insulin secretion (14).…”

“…Increased NL-2 expression caused increased insulin secretion, and decreased expression lowered insulin secretion (14). In work done elsewhere (15), NL-2 was one of the most abundant transcripts identified in a systematic study of human tissue mRNAs that was carried out in order to identify highly expressed, human islet-specific membrane proteins.…”