Latrophilins and Teneurins in Invertebrates: No Love for Each Other?

Abstract

Transsynaptic connections enabling cell–cell adhesion and cellular communication are a vital part of synapse formation, maintenance and function. A recently discovered interaction between the Adhesion GPCRs Latrophilins and the type II single transmembrane proteins Teneurins at mammalian synapses is vital for synapse formation and dendrite branching. While the understanding of the effects and the molecular interplay of this Latrophilin-Teneurin partnership is not entirely understood, its significance is highlighted by behavioral and neurological phenotypes in various animal models. As both groups of molecules, Latrophilins and Teneurins, are generally highly conserved, have overlapping expression and often similar functions across phyla, it can be speculated that this interaction, which has been proven essential in mammalian systems, also occurs in invertebrates to control shaping of synapses. Knowledge of the generality of this interaction is especially of interest due to its possible involvement in neuropathologies. Further, several invertebrates serve as model organisms for addressing various neurobiological research questions. So far, an interaction of Latrophilins and Teneurins has not been observed in invertebrates, but our knowledge on both groups of molecules is by far not complete. In this review, we give an overview on existing experimental evidence arguing for as well as against a potential Latrophilin-Teneurin interaction beyond mammals. By combining these insights with evolutionary aspects on each of the interaction partners we provide and discuss a comprehensive picture on the functions of both molecules in invertebrates and the likeliness of an evolutionary conservation of their interaction.

Revisiting the classification of adhesion GPCRs

“…For instance, thus far the Drosophila homolog CG8639/Cirl has been associated with vertebrate latrophilins. Several ligands have been described for mammalian latrophilins (teneurins, FLRTs, and neurexin‐1β); however, to date, no evidence for an interaction between the orthologous invertebrate ligand candidates and invertebrate latrophilins/dmCirl has been obtained yet . While the extracellular region of vertebrate latrophilins and dmCIRL contains rhamnose‐binding lectin and hormone receptor motif domains, the latter lacks the olfactomedin domain, which is required for biochemical interactions of vertebrate latrophilins with neurexin‐1β and FLRT.…”

Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

“…Of the specifically bound proteins that interact directly or indirectly in a complex with Toll-8, Cirl was the most abundant target (Figure 3B; Table S1) and of particular interest since it is a GPCR. Cirl is the Drosophila homolog of vertebrate latrophilin, a member of the adhesion GPCR (aGPCR) subfamily (Scholz et al, 2015;Schö neberg and Prö mel, 2019). Interestingly, the Toll-8 extracellular domain shares sequence similarities with that of the human LRR protein FLRTs (Dolan et al, 2007), which are known to form protein complexes with human latrophilins (Boucard et al, 2014;Li et al, 2020;O'Sullivan et al, 2012;Sando et al, 2019;del Toro et al, 2020).…”

Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

“…Of the specifically bound proteins, Cirl was the most abundant target ( Figure 3B and Table 1) and of particular interest since it is a G protein-coupled receptor (GPCR). Cirl is the Drosophila homologue of vertebrate Latrophilin, a member of the adhesion GPCR (aGPCR) subfamily (Scholz et al, 2015;Schöneberg and Prömel, 2019). Interestingly, the Toll-8 extracellular domain shares sequence similarities with the extracellular domains of the human LRR proteins FLRTs (Dolan et al, 2007), which are known to form protein complexes with human Latrophilins (Boucard et al, 2014;O'Sullivan et al, 2012;Sando et al, 2019;del Toro et al, 2020).…”