Identification of an oxytocinase/vasopressinase-like leucyl-cystinyl aminopeptidase (LNPEP) in teleost fish and evidence for hypothalamic mRNA expression linked to behavioral social status

Elkins, Emma A; Walti, Kayla A.; Newberry, Kathryn E.; Lema, Sean C.

doi:10.1016/j.ygcen.2017.06.002

Cited by 12 publications

(13 citation statements)

References 87 publications

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“…Further studies confirmed the almost ubiquitous IRAP expression and its involvement in a variety of physiological processes, such as antigen cross-presentation by major histocompatibility class I (MHC-I) molecules (Saveanu et al, 2009;Segura et al, 2009;Weimershaus et al, 2012), endosomal Toll-like receptor (TLR) signaling (Babdor et al, 2017), lactation (Tobin et al, 2014), cognition (Banegas et al, 2010;Elkins et al, 2017), and stress responses (Hernández et al, 2015). During the investigation of these various functions, it became evident that in all cell types analyzed, IRAP is localized in intracellular vesicles reminiscent of adipocyte GSV that we proposed to call "cell-specific storage endosomes" (Saveanu and van Endert, 2012).…”

Section: Irap Identification and Tissue Expressionmentioning

confidence: 86%

The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells

Descamps

Evnouchidou

Caillens

et al. 2020

Front. Mol. Biosci.

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Insulin regulated aminopeptidase (IRAP) is a type II transmembrane protein with broad tissue distribution initially identified as a major component of Glut4 storage vesicles (GSV) in adipocytes. Despite its almost ubiquitous expression, IRAP had been extensively studied mainly in insulin responsive cells, such as adipocytes and muscle cells. In these cells, the enzyme displays a complex intracellular trafficking pattern regulated by insulin. Early studies using fusion proteins joining the IRAP cytosolic domain to various reporter proteins, such as GFP or the transferrin receptor (TfR), showed that the complex and regulated trafficking of the protein depends on its cytosolic domain. This domain contains several motifs involved in IRAP trafficking, as demonstrated by mutagenesis studies. Also, proteomic studies and yeast two-hybrid experiments showed that the IRAP cytosolic domain engages in multiple protein interactions with cytoskeleton components and vesicular trafficking adaptors. These findings led to the hypothesis that IRAP is not only a cargo of GSV but might be a part of the sorting machinery that controls GSV dynamics. Recent work in adipocytes, immune cells, and neurons confirmed this hypothesis and demonstrated that IRAP has a dual function. Its carboxy-terminal domain located inside endosomes is responsible for the aminopeptidase activity of the enzyme, while its amino-terminal domain located in the cytosol functions as an endosomal trafficking adaptor. In this review, we recapitulate the published protein interactions of IRAP and summarize the increasing body of evidence indicating that IRAP plays a role in intracellular trafficking of several proteins. We describe the impact of IRAP deletion or depletion on endocytic trafficking and the consequences on immune cell functions. These include the ability of dendritic cells to cross-present antigens and prime adaptive immune responses, as well as the control of innate and adaptive immune receptor signaling and modulation of inflammatory responses.

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Section: Irap Identification and Tissue Expressionmentioning

confidence: 86%

The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells

Descamps

Evnouchidou

Caillens

et al. 2020

Front. Mol. Biosci.

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“…After~5 mo in captivity, pupfish (n ϭ 3 for each sex) were netted, euthanized using tricaine methansulfonate (MS222; 300 mg/l in water buffered with 200 mg/l NaHCO 3), and the following tissues were dissected, flash-frozen in liquid N2, and stored at Ϫ80°C: brain, pituitary gland, gills, heart, liver, gonads, kidney, gastrointestinal (GI) tract, and muscle (collected from the left side of the caudal peduncle). The brain was subdivided into the telencephalon, hypothalamus, optic tectum, cerebellum, and hindbrain (medulla oblongata) regions before freezing, as described by Elkins et al (16). The sex of each pupfish was determined by visually assessing gonadal sex.…”

Section: Tissue Distribution Patterns Of Avt and It Receptor Transcript Abundancementioning

confidence: 99%

“…For each gene, relative mRNA levels were normalized to mRNA abundance values for ␤-actin in each tissue, and abundance values of each gene of interest were then expressed as a relative level by dividing resulting values by the mean expression level of that gene in the forebrain tissue of male pupfish. Results showing the distribution of lnpep mRNAs in these same fish are provided in Elkins et al (16).…”

Section: Tissue Distribution Patterns Of Avt and It Receptor Transcript Abundancementioning

confidence: 99%

“…To gain a more comprehensive picture of nonapeptide actions in the gill during salinity acclimation, we also examined transcriptional changes in the leucyl-cystinyl aminopeptidase (LNPEP) enzyme, also known as vasopressinase or oxytocinase, a membrane-bound, zinc-dependent metalloexopeptidase that inactivates nonapeptides of the AVT/IT family as well as selected other cyclic polypeptides (62,94). A complementary DNA (cDNA) encoding this putative AVT/IT degradation enzyme was recently identified in Amargosa pupfish, and messenger RNAs (mRNAs) for lnpep were found to be at relatively high levels in the gill (16). We therefore also examined whether transcripts encoding LN-PEP vary in the gill in patterns indicative of expressional regulation by hyper-or hypoosmotic conditions.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for a role of arginine vasotocin receptors in the gill during salinity acclimation by a euryhaline teleost fish

Lema

Washburn

Crowley

et al. 2019

American Journal of Physiology-Regulatory, Integrative and Comp

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The nonapeptide arginine vasotocin (AVT) regulates osmotic balance in teleost fishes, but its mechanisms of action are not fully understood. Recently, it was discovered that nonapeptide receptors in teleost fishes are differentiated into two V1a-type, several V2-type, and two isotocin (IT) receptors, but it remains unclear which receptors mediate AVT’s effects on gill osmoregulation. Here, we examined the role of nonapeptide receptors in the gill of the euryhaline Amargosa pupfish ( Cyprinodon nevadensis amargosae) during osmotic acclimation. Transcripts for the teleost V1a-type receptor v1a2 were upregulated over fourfold in gill 24 h after transferring pupfish from 7.5 ppt to seawater (35 ppt) or hypersaline (55 ppt) conditions and downregulated after transfer to freshwater (0.3 ppt). Gill transcripts for the nonapeptide degradation enzyme leucyl-cystinyl aminopeptidase (LNPEP) also increased in fish acclimating to 35 ppt. To test whether the effects of AVT on the gill might be mediated by a V1a-type receptor, we administered AVT or a V1-type receptor antagonist (Manning compound) intraperitoneally to pupfish before transfer to 0.4 ppt or 35 ppt. Pupfish transferred to 35 ppt exhibited elevated gill mRNA abundance for cystic fibrosis transmembrane conductance regulator ( cftr), but that upregulation diminished under V1-receptor inhibition. AVT inhibited the increase in gill Na+/Cl− cotransporter 2 ( ncc2) transcript abundance that occurs following transfer to hypoosmotic environments, whereas V1-type receptor antagonism increased ncc2 mRNAs even without a change in salinity. These findings indicate that AVT acts via a V1-type receptor to regulate gill Cl− transport by inhibiting Cl− uptake and facilitating Cl− secretion during seawater acclimation.

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“…These behavioural changes are accompanied by pronounced and prolonged structural modifications in several brain regions implicated in social cognition, namely parts of prefrontal, parietal and superior temporal cortices (16). Although already present in the prenatal developing brain, preclinical evidence suggests that the expression of the receptors of AVP (arginine vasopressin receptor 1A (LNPEP), a molecular player involved in OT release (21) and one of the enzymes responsible for both OT and AVP degradation (22). Considering that, at least in the brain, several elements of these nonapeptides' machinery seem to dynamically evolve during the post-natal period, one may speculate these changes are functionally relevant and underpin significant differences between OT/AVP impacts on behaviour during different developmental periods.…”

Section: Introductionmentioning

confidence: 99%

How do hypothalamic nonapeptides shape youth’s sociality? A systematic review on oxytocin, vasopressin and human socio-emotional development

Torres

Martins

Santos

et al. 2018

Neuroscience & Biobehavioral Reviews

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The hypothalamic nonapeptides oxytocin and vasopressin are important modulators of socio-affective behaviours in a wide variety of animal species, including humans. Nevertheless, there is little research addressing their possible roles on socio-affective dimensions of human behaviour across development, during which considerable behavioural and physiological change occurs. Questions still remain about the extent to which findings from adults may directly apply to earlier phases of human development. In this article, we systematically summarize and discuss all existing studies investigating the developmental association of endogenous levels of hypothalamic neuropeptides oxytocin and vasopressin with human social behaviour or on its disruption in paediatric populations. Evidence is sparse insofar as there are still relatively few developmental studies and limited due to correlational research designs and unreliability of methods currently used for neuropeptide measurements in biological fluids. The findings to date generally converge with adult evidence, but also suggest that important differences between age stages may exist. Further studies focusing these differences may prove critical for informing drug development for socio-affective deficits in paediatric populations.

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Identification of an oxytocinase/vasopressinase-like leucyl-cystinyl aminopeptidase (LNPEP) in teleost fish and evidence for hypothalamic mRNA expression linked to behavioral social status

Cited by 12 publications

References 87 publications

The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells

The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells

Evidence for a role of arginine vasotocin receptors in the gill during salinity acclimation by a euryhaline teleost fish

How do hypothalamic nonapeptides shape youth’s sociality? A systematic review on oxytocin, vasopressin and human socio-emotional development

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