PT  - JOURNAL ARTICLE
AU  - Chiara Camillo
AU  - Nicola Facchinello
AU  - Dafne Gays
AU  - Giulia Villari
AU  - Noemi Gioelli
AU  - Chiara Sandri
AU  - Marco Arese
AU  - Luca Tamagnone
AU  - Donatella Valdembri
AU  - Massimo Santoro
AU  - Guido Serini
TI  - Latrophilin 2 controls vascular morphogenesis and function by inhibiting endothelial cell adhesion and YAP/TAZ mechanosignaling
AID  - 10.1101/2020.04.28.065979
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.28.065979
4099  - http://biorxiv.org/content/early/2020/04/28/2020.04.28.065979.short
4100  - http://biorxiv.org/content/early/2020/04/28/2020.04.28.065979.full
AB  - Dynamic modulation of endothelial cell (EC) adhesion to extracellular matrix (ECM) in response to mechanostimuli is essential for blood vessel patterning and functioning. Yet, the molecular mechanisms involved in this biological process are far to be completely deciphered. Here, we identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of vascular morphogenesis and endothelial barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM adhesions, signals through cAMP/Rap1, and, via its fibronectin-leucine-rich transmembrane (FLRT)-binding domain, negatively regulates ECM-elicited haptotaxis. ECs also express endogenous FLRT2 ligand that promotes cAMP/Rap1 signaling and hinders haptotaxis in a LPHN2-dependent manner. Vascular ECs of lphn2a knock-out zebrafish embryos become abnormally stretched, display a hyperactive Hippo mechanosensing pathway, and lack proper intercellular junctions. Indeed, intravascularly injected cancer cells extravasate more easily in lphn2a null animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.