The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions.
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 beta-neurexin inhibits angiogenesis, whereas exogenous neuroligin has a role in promoting angiogenesis. Finally, as an insight into the mechanism of action of beta-neurexin, we show that the anti-beta-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.
Bottos
Alessia
A
Department of Oncological Sciences and Institute for Cancer Research and Treatment, University of Torino School of Medicine, 10060 Candiolo (TO), Italy.
Destro
Erika
E
Rissone
Alberto
A
Graziano
Stefania
S
Cordara
Gabriele
G
Assenzio
Barbara
B
Cera
Maria Rosaria
MR
Mascia
Luciana
L
Bussolino
Federico
F
Arese
Marco
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; D019006:Neural Cell Adhesion Molecules; C093438:neuroligin 1