The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions

Abstract

Unlike other neuronal counterparts, primary synaptic proteins are not known to be involved in vascular physiology. Here, we demonstrate that neurexins and neuroligins, which constitute large and complex families of fundamental players in synaptic activity, are produced and processed by endothelial and vascular smooth muscle cells throughout the vasculature. Moreover, they are dynamically regulated during vessel remodeling and form endogenous complexes in large vessels as well as in the brain. We used the chicken chorioallantoic membrane as a system to pursue functional studies and demonstrate that a monoclonal recombinant antibody against ␤-neurexin inhibits angiogenesis, whereas exogenous neuroligin has a role in promoting angiogenesis. Finally, as an insight into the mechanism of action of ␤-neurexin, we show that the anti-␤-neurexin antibody influences vessel tone in isolated chicken arteries. Our finding strongly supports the idea that even the most complex and plastic events taking place in the nervous system (i.e., synaptic activity) share molecular cues with the vascular system. angiogenesis ͉ vessel tone ͉ cell-to-cell adhesion ͉ nervous-vascular parallels ͉ synapses

The Synaptic Proteins β-Neurexin and Neuroligin Synergize With Extracellular Matrix-Binding Vascular Endothelial Growth Factor A During Zebrafish Vascular Development

“…15 Nevertheless, we recently demonstrated that NRXNs and NLGNs are expressed in the vascular system and contribute to its function. 16 In parallel, we identified the members of zebrafish (Danio rerio) NRXN and NLGN gene families. 17,18 To deepen the functional characterization of these 2 gene families in vascular development, we took advantage of the zebrafish model system to perform an in vivo study.…”

“…17,18 To deepen the functional characterization of these 2 gene families in vascular development, we took advantage of the zebrafish model system to perform an in vivo study. Given the lack of in vivo functional data for β-NRXNs and starting from our previous findings, 16 we focused our analyses on the β-nrxn1a and nlgn1 genes. Expression analyses indicate that both genes are expressed in endothelial and mesenchymal cells of the trunk/tail region of zebrafish embryos.…”

Neuroligin 1 Induces Blood Vessel Maturation by Cooperating with the α6 Integrin

“…The ␣6 integrin-Myc pWpXL lentivirus was produced as described (7). The day before the infection, ECs were seeded at concentrations of 3.5 ϫ 10 4 cells/ml in a 10-cm 2 tissue culture dish.…”

“…Recently, we have demonstrated that they have a function in vascular biology (7), and that a mature ECM has a pivotal role in vascular development and angiogenesis (7)(8)(9). In particular, the use of a zebrafish model combined with the knockdown of multiple genes (8) suggested that ECM is a critical component of NLGN signaling during vascular development, allowing the organization of ECM-immobilized vascular endothelial growth factor-A (VEGFA) gradients necessary for capillary networking (10) (11).…”

“…The extracellular matrix (ECM) 7 provides essential support for the growth and organization of blood vessels (1). During sprouting angiogenesis, endothelial cells (ECs) secrete matrix proteins such as vitronectin, fibronectin, and collagen I leading to the formation of a provisional ECM, which sustains ECs proliferation and migration (2).…”