Structural highlights
Function
[LPHN3_MOUSE] May be involved in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.[1]
Publication Abstract from PubMed
Latrophilins, receptors for spider venom alpha-latrotoxin, are adhesion type G-protein-coupled receptors with emerging functions in synapse development. The N-terminal region binds the endogenous cell adhesion molecule FLRT, a major regulator of cortical and synapse development. We present crystallographic data for the mouse Latrophilin3 lectin and olfactomedin-like (Olf) domains, thereby revealing the Olf beta-propeller fold and conserved calcium-binding site. We locate the FLRT-Latrophilin binding surfaces by a combination of sequence conservation analysis, point mutagenesis, and surface plasmon resonance experiments. In stripe assays, we show that wild-type Latrophilin3 and its high-affinity interactor FLRT2, but not the binding-impaired mutants we generated, promote HeLa cell adhesion. In contrast, cortical neurons expressing endogenous FLRTs are repelled by wild-type Latrophilin3 and not by the binding-impaired mutant. Taken together, we present molecular level insights into Latrophilin structure, its FLRT-binding mechanism, and a role for Latrophilin and FLRT that goes beyond a simply adhesive interaction.
Structural Basis of Latrophilin-FLRT Interaction.,Jackson VA, Del Toro D, Carrasquero M, Roversi P, Harlos K, Klein R, Seiradake E Structure. 2015 Feb 17. pii: S0969-2126(15)00037-4. doi:, 10.1016/j.str.2015.01.013. PMID:25728924[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ O'Sullivan ML, Martini F, von Daake S, Comoletti D, Ghosh A. LPHN3, a presynaptic adhesion-GPCR implicated in ADHD, regulates the strength of neocortical layer 2/3 synaptic input to layer 5. Neural Dev. 2014 Apr 17;9:7. doi: 10.1186/1749-8104-9-7. PMID:24739570 doi:http://dx.doi.org/10.1186/1749-8104-9-7
- ↑ Jackson VA, Del Toro D, Carrasquero M, Roversi P, Harlos K, Klein R, Seiradake E. Structural Basis of Latrophilin-FLRT Interaction. Structure. 2015 Feb 17. pii: S0969-2126(15)00037-4. doi:, 10.1016/j.str.2015.01.013. PMID:25728924 doi:http://dx.doi.org/10.1016/j.str.2015.01.013
