Latrophilin‐2 is a novel component of the epithelial‐mesenchymal transition within the atrioventricular canal of the embryonic chicken heart

Abstract

Endothelial cells in the atrioventricular canal of the heart undergo an epithelial-mesenchymal transition (EMT) to form heart valves. We surveyed an on-line database (http://www.geisha.arizona.edu/) for clones expressed during gastrulation to identify novel EMT components. One gene, latrophilin-2, was identified as expressed in the heart and appeared to be functional in EMT. This molecule was chosen for further examination. In situ localization showed it to be expressed in both the myocardium and endothelium. Several antisense DNA probes and an siRNA for latrophilin-2 produced a loss of EMT in collagen gel cultures. Latrophilin-2 is a putative G-protein-coupled receptor and we previously identified a pertussis toxin-sensitive G-protein signal transduction pathway. Microarray experiments were performed to examine whether these molecules were related.

Comparative Expression Study of the Endo–G Protein Coupled Receptor (GPCR) Repertoire in Human Glioblastoma Cancer Stem-like Cells, U87-MG Cells and Non Malignant Cells of Neural Origin Unveils New Potential Therapeutic Targets

“…LPHN2 is an adhesion GPCR (group I) belonging to the family of latrophilins composed of three members (LPHN1-3) (for review see [140]). Expression of latrophilin 1 and 3 is mainly found in the central nervous system, whereas LPHN2 is more ubiquitous [140], [141], [142], [143]. LPHN2 shares with the two other members a large N-terminus composed of lectin, olfactomedin and hormone binding domains.…”

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

“…ADGRL2 (latrophilin-2) expression is required for normal epithelial-mesenchymal transition of endothelial cells in the atrioventricular canal of the heart during early chick development; however, it is unclear how ADGRL2 (latrophilin-2) controls this transition (Doyle et al, 2006). In zebrafish and mice, ADGRG6 (GPR126) signaling is required for Schwann cell differentiation, as elevation of cAMP mediated by ADGRG6 (GPR126) is necessary for the terminal differentiation of myelinating Schwann cells (Monk et al, 2009(Monk et al, , 2011Glenn and Talbot, 2013;Mogha et al, 2013).…”

“…Several Adhesion GPCRs are associated with the cardiovascular system. ADGRL2 (latrophilin-2) is required for heart valve formation, acting as a component of the epithelialmesenchymal transition in the atrioventricular canal 354 (Doyle et al, 2006). ADGRL1 (latrophilin-1) expression has been detected during rat heart development, but its function is unclear (Ferrand et al, 1999).…”

Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation

“…Also, orphan receptor latrophilin-2 (encoded by Lphn2) was upregulated in ECsc derived from EAE mice, but in contrast to F2r and Darc, it was rather associated with a less-activated endothelial phenotype. The latrophilin family of adhesion receptors has been implicated in regulation of cell-cell and cell-matrix interactions, but data regarding specific cellular functions of LPHN2 are, except for a putative role in EMT, lacking (57,58). Our knockdown experiments in human brain EC showed that loss of LPHN2 results in increased expression of mediators implicated in leukocyte adhesion and transmigration through the endothelial barrier, such as IL-8 (59), CXCL11 (60), CXCL12 (61), or chemokine binding proteins syndecan and CD44 (37).…”