The Latrophilins, “Split-Personality” Receptors

Silva, John-Paul; Ushkaryov, Yuri A.

doi:10.1007/978-1-4419-7913-1_5

Cited by 49 publications

(47 citation statements)

References 76 publications

(175 reference statements)

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“…In contrast to these results, the structure of GAIN domain suggests that the site of cleavage is buried within a rigid domain structure, and the resulting subunits cannot be easily detached or recombined unless the protein is substantially denatured (84). This also accounts for the high structural similarity between GAIN domains of noncleavable and cleavable AdhesionGPCRs (38).…”

Section: Adhesion-gpcrs-receptors With Split Personality?mentioning

confidence: 81%

“…Phosphorylation of Adhesion-GPCRs that couple to G proteins such as latrophilin 1 and GPR56 is demonstrated (60,84,130,134). The CTF of latrophilin 1 is phosphorylated in rat brain but not in cultured cells, suggesting that phosphorylation occurs in vivo, perhaps as a result of physiological brain function that cannot be recapitulated in vitro (84).…”

Section: Phosphorylation Of the Ctfmentioning

confidence: 99%

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Sticky Signaling—Adhesion Class G Protein–Coupled Receptors Take the Stage

2013

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Adhesion-type heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (Adhesion-GPCRs) comprise a class of widely distributed seven-transmembrane spanning (7TM) receptors with unusual layout and properties. The key to understanding the function of Adhesion-GPCRs appears to be their hybrid architecture: They have an extracellular domain containing an extended array of protein folds fit for interactions, and structural elements of GPCRs with a 7TM and an intracellular domain. If and how these distinct protein portions interact is currently under intense investigation. Intriguingly, all Adhesion-GPCRs have a juxtamembrane GPCR autoproteolysis-inducing domain that, in many homologs, facilitates the autocatalytic processing into an N-terminal fragment (NTF) and a C-terminal fragment (CTF), which subsequently remain attached at the cell surface. The NTF provides the ability for combinatorial engagement with cellular or matrix-associated molecules facilitating cell adhesion, orientation, and positioning during development, immune responses, and tumor growth. The CTF, like in canonical GPCRs, initiates interactions with different types of signaling molecules, including heterotrimeric G proteins, small guanosine triphosphatases, and transmembrane protein partners, yet the agonistic potential of most known Adhesion-GPCR ligands is uncertain. Studies with truncated receptors suggest that the NTF and CTF of Adhesion-GPCRs may function as autonomous adhesive and signaling units, respectively, but other studies in nonvertebrates demonstrating NTF-CTF interplay challenge this view. We discuss the available data concerning the main structural elements of Adhesion-GPCRs in the context of receptor function and signaling.

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Section: Adhesion-gpcrs-receptors With Split Personality?mentioning

confidence: 81%

Section: Phosphorylation Of the Ctfmentioning

confidence: 99%

Sticky Signaling—Adhesion Class G Protein–Coupled Receptors Take the Stage

2013

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“…However, this region is contained in the Stalk domain needed to bind its ligand, -latrotoxin (Krasnoperov et al 1999;Silva & Ushkaryov 2010). The in silico analysis suggested a role of this region as ESEs, which are discrete sequences within exons that promote both constitutive and alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

LPHN3 and attention‐deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study

Bruxel

Salatino-Oliveira

Akutagava-Martins

et al. 2015

Genes Brain and Behavior

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Latrophilin 3 (LPHN3) is a brain-specific member of the G-protein coupled receptor family associated to both attention-deficit/hyperactivity disorder (ADHD) genetic susceptibility and methylphenidate (MPH) pharmacogenetics. Interactions of LPHN3 variants with variants harbored in the 11q chromosome improve the prediction of ADHD development and medication response. The aim of this study was to evaluate the role of LPHN3 variants in childhood ADHD susceptibility and treatment response in a naturalistic clinical cohort. The association between LPHN3 and ADHD was evaluated in 523 children and adolescents with ADHD and 132 controls. In the pharmacogenetic study, 172 children with ADHD were investigated. The primary outcome measure was the parent-rated Swanson, Nolan and Pelham Scale -version IV applied at baseline, first and third months of treatment with MPH. The results reported herein suggest the CGC haplotype derived from single nucleotide polymorphisms (SNPs) rs6813183, rs1355368 and rs734644 as an ADHD risk haplotype (P = 0.02, OR = 1.46). Although non-significant after multiple testing correction, its interaction with the 11q chromosome SNP rs965560 slightly increases risk (P = 0.03, OR = 1.55). Homozygous individuals for the CGC haplotype showed faster response to MPH treatment as a significant interaction effect between CGC haplotype and treatment over time was observed (P < 0.001). Homozygous individuals for the GT haplotype derived from SNPs rs6551665 and rs1947275 showed a nominally significant interaction with treatment over time (P = 0.04). Our findings replicate previous findings reporting that LPHN3 confers ADHD susceptibility, and moderates MPH treatment response in children and adolescents with ADHD.

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“…Latrophilin receptors, a neuronal adhesion G-protein-coupled receptor, was the other class B GPCR identified in the study. Previous studies in nematodes have shown that it controls neurotransmitter release on binding with specific ligands in adult brains (Silva et al, 2010). Indepth study of latrophilin-related GPCR signaling pathway in An.…”

Section: Enrichment Of Gpcrs In the Brain Studymentioning

confidence: 99%

Brain Proteomics of Anopheles gambiae

Dwivedi

Muthusamy

Kumar

et al. 2014

OMICS: A Journal of Integrative Biology

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Anopheles gambiae has a well-adapted system for host localization, feeding, and mating behavior, which are all governed by neuronal processes in the brain. However, there are no published reports characterizing the brain proteome to elucidate neuronal signaling mechanisms in the vector. To this end, a large-scale mapping of the brain proteome of An. gambiae was carried out using high resolution tandem mass spectrometry, revealing a repertoire of >1800 proteins, of which 15% could not be assigned any function. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including metabolism, transport, protein synthesis, and olfaction. This study also led to the identification of 10 GPCR classes of proteins, which could govern sensory pathways in mosquitoes. Proteins involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission were predominantly expressed in the brain. Proteogenomic analysis expanded our findings with the identification of 15 novel genes and 71 cases of gene refinements, a subset of which were validated by RT-PCR and sequencing. Overall, our study offers valuable insights into the brain physiology of the vector that could possibly open avenues for intervention strategies for malaria in the future.

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The Latrophilins, “Split-Personality” Receptors

Cited by 49 publications

References 76 publications

Sticky Signaling—Adhesion Class G Protein–Coupled Receptors Take the Stage

Sticky Signaling—Adhesion Class G Protein–Coupled Receptors Take the Stage

LPHN3 and attention‐deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study

Brain Proteomics of Anopheles gambiae

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