Neurexins and neuroligins: synapses look out of the nervous system

Abstract

The scientific interest in the family of the so-called nervous vascular parallels has been growing steadily for the past 15 years, either by addition of new members to the group or, lately, by deepening the analysis of established concepts and mediators. Proteins governing both neurons and vascular cells are known to be involved in events such as cell fate determination and migration/guidance but not in the last and apparently most complex step of nervous system development, the formation and maturation of synapses. Hence, the recent addition to this family of the specific synaptic proteins, Neurexin and Neuroligin, is a double innovation. The two proteins, which were thought to be "simple" adhesive links between the pre- and post-synaptic sides of chemical synapses, are in fact extremely complex and modulate the most subtle synaptic activities. We will discuss the relevant data and the intriguing challenge of transferring synaptic activities to vascular functions.

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

“…Neurexins (NRXNs) 1 are a family of pre-synaptic transmembrane proteins involved in the modulation of synaptic activity in partnership with the post synaptic Neuroligins (NLGNs). In mammals, there are 3 different NRXN genes, each presenting 2 alternative promoters which drive the synthesis of 2 major isoforms per gene (a long αNRXN, and a short C-terminal βNRXN).…”

“…We recently discovered that a)  and NRXN as well as NLGN are expressed by blood vessels b) NRXN and NLGN modulate angiogenesis in the chick embryo chorioallantoic membrane assay; c) while both NRXN and NRXN co-precipitate with NLGN in brain, only NRXNdoes so in blood vessels [1]d) in zebrafish NRXN but not NRXN knock-down causes vascular defect in synergy with VEGFA [2]. All these findings raise questions about NRXN function and protein partners in the vascular system.…”

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

“…4E). Interestingly, all three distinct interacting partners of the latrophilinsteneurins, FLRTs, and neurexins-are single-span transmembrane molecules that have roles in axon guidance, neuronal connectivity, and synapse formation (Lise and El-Husseini, 2006;Tucker et al, 2007;Bottos et al, 2011;O'Sullivan et al, 2012). This suggests that latrophilins have a general role in recognizing transmembranous molecules involved in neuronal biology and may function to signal during neuronal development mediated via interactions with these binding partners.…”

Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

“…The NGL-Netrin-G complexes have been crystallized, and the structural models show that the convex part of the NGL LRR domains interacts with the Ig module of the same molecule. Consequently, the concave part of the NGL LRR domains is exposed to the surrounding environment, allowing it to interact with the N-terminal Laminin domains of Netrin-G proteins (Seiradake et al 2011 ;Brasch et al 2011 ) (Fig. 14.4 ).…”

“…However, within recent years several other protein families with members able to mediate homo-or heterophilic cell adhesion have been identifi ed. These include for instance Neurexins and Neuroligins (Bottos et al 2011 ). Moreover, the family of leucine-rich repeat (LRR)-containing proteins includes numerous CAMs (Nam et al 2011 ;Woo et al 2009a ;Karaulanov et al 2006 ;Hohenester 2008 ).…”