6ske | pdb_00006ske
Teneurin 2 in complex with Latrophilin 2 Lec domain
Structural highlights
Function[TEN2_CHICK] Acts as a ligand of the ADGRL1 receptor (By similarity). Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Promotes the formation of filopodia and enlarged growth cone in neuronal cells. Induces homophilic cell-cell adhesion. May also mediates axon guidance and heterophilic cell-cell adhesion. May function as a cellular signal transducer.[1] [2] [3] Ten-2 intracellular domain: Induces gene transcription inhibition. [AGRL2_MOUSE] Calcium-independent receptor of low affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis.[UniProtKB:O88923][4] Publication Abstract from PubMedTeneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the adhesion GPCR Latrophilin, forming a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, and FLRT proteins are also expressed during murine cortical cell migration at earlier developmental stages. Here, we present crystal structures of Teneurin-Latrophilin complexes that reveal how the lectin and olfactomedin domains of Latrophilin bind across a spiraling beta-barrel domain of Teneurin, the YD shell. We couple structure-based protein engineering to biophysical analysis, cell migration assays, and in utero electroporation experiments to probe the importance of the interaction in cortical neuron migration. We show that binding of Latrophilins to Teneurins and FLRTs directs the migration of neurons using a contact repulsion-dependent mechanism. The effect is observed with cell bodies and small neurites rather than their processes. The results exemplify how a structure-encoded synaptogenic protein complex is also used for repulsive cell guidance. Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons.,Del Toro D, Carrasquero-Ordaz MA, Chu A, Ruff T, Shahin M, Jackson VA, Chavent M, Berbeira-Santana M, Seyit-Bremer G, Brignani S, Kaufmann R, Lowe E, Klein R, Seiradake E Cell. 2020 Jan 23;180(2):323-339.e19. doi: 10.1016/j.cell.2019.12.014. Epub 2020 , Jan 9. PMID:31928845[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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