From the black widow spider to human behavior: Latrophilins, a relatively unknown class of G protein‐coupled receptors, are implicated in psychiatric disorders

Abstract

The findings of a recent study associate LPHN3, a member of the latrophilin family, with an increased risk of developing attention deficit/hyperactivity disorder (ADHD), the most common psychiatric disorder in childhood and adolescence. Latrophilins comprise a new family of G protein-coupled receptors of unknown native physiological function that mediate the neurotoxic effects of α-latrotoxin, a potent toxin found in black widow spider venom. This receptor–toxin interaction has helped to elucidate the mechanistic aspects of neurotransmitter and hormone release in vertebrates. Such unprecedented discovery points to a new direction in the assessment of ADHD and suggest that further study of this receptor family may provide novel insights into the etiology and treatment of ADHD and other related psychiatric conditions.

Quantitative Real-Time RT-PCR of ITGA7, SVEP1, TNS1, LPHN3, SEMA3G, KLB and MMP13 mRNA Expression in Breast Cancer

“…This study found that increased mRNA expression of LPHN3 and MMP13 in breast-cancer tissues significantly correlated with axillary lymph node positivity, which was particularly interesting. LPHN3 (the latrophilin 3 gene) is a member of the G-protein coupled receptor (GPCR) family; it has large extracellular and intracellular domains, containing several cell adhesion modules, such as cadherin, IgG, laminin A, thrombospondin type 1, galactose lectin, EGF, and transmembrane segments that may be involved in intracellular signalling during cell-to-cell adhesion (Martinez et al, 2011). LPHN3 was up-regulated significantly in a transgenic mice model that over-expressed myocilin (Paper et al, 2008).…”

“…These genes play a role in cell adhesion and migration (Elnemr et al, 2003;Shur et al, 2007;Karayan-Tapon et al, 2008;Hall et al, 2009;Zhu et al, 2010;Martinez et al, 2011;. Moreover, the association between mRNA expression and the clinical characteristics of these patients was evaluated.…”

Interplay between supramodal attentional control and capacity limits in the low-level visual processors modulate the tendency to inattention

“…However, the reason why distractors are attended is still unknown. Some studies have proposed a link between the tendency to present low level of inattention and ADHD (see for example Arcos-Burgos et al, 2010;Grossman, Hoffman, Berger, & Zivotofsky, 2015;Martinez, Muenke, & Arcos-Burgos, 2011;Papera & Richards, 2016;Ribasés et al, 2010). Although still controversial, since a number of studies discuss an impairment during visual search in ADHD subjects (Fallgatter et al, 2013;Maccari et al, 2013), ADHD individuals may present an alternative perceptual style which is less equipped to deal with detection of repeated stimuli, but more adapted to reorient/allocate visual-spatial attention towards unexpected stimuli (Couperus, Alperin, Furlong, & Mott, 2014;Grossman et al, 2015).…”

“…Although still controversial, since a number of studies discuss an impairment during visual search in ADHD subjects (Fallgatter et al, 2013;Maccari et al, 2013), ADHD individuals may present an alternative perceptual style which is less equipped to deal with detection of repeated stimuli, but more adapted to reorient/allocate visual-spatial attention towards unexpected stimuli (Couperus, Alperin, Furlong, & Mott, 2014;Grossman et al, 2015). This also appears to receive support from genetic studies, which showed that nucleotide polymorphism variants for the LPHN3 that confer ADHD susceptibility are older than the LPHN3 allelic variant that protects against ADHD (Ribasés et al, 2010;Arcos-Burgos et al, 2010;Martinez et al, 2011). Therefore, it may be conceivable that this type of scene exploration (anticipation of extra stimuli) may have provided some advantage in evolutionary terms.…”

Influence of a Latrophilin 3 (LPHN3) risk haplotype on event-related potential measures of cognitive response control in attention-deficit hyperactivity disorder (ADHD)

“…A possible relationship of FLRT3 copy number variations with ADHD (Lionel et al, 2011) hints at a putative mechanism mediating the development of ADHD symptoms. As LPHN3 is expressed in brain structures belonging to the nigrostriatal, the mesolimbic, and the mesocortical dopaminergic systems (Martinez et al, 2011), interaction with prefrontal cortex activity is quite likely and may explain differences in the investigated neurophysiological marker. However, these preliminary findings—without further support from in-vitro and in-vivo studies—have yet to be considered with caution.…”