Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand

Moriwaki, Yuji; Watanabe, Y.; Shinagawa, Tomoe; Kai, Miho; Miyazawa, Mai; Okuda, Takashi; Kawashima, Koichiro; Yabashi, Atsuko; Waguri, Satoshi; Misawa, Hidemi

doi:10.1016/j.neures.2009.04.014

Cited by 58 publications

(55 citation statements)

References 36 publications

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“…In addition to skin, SLURPs are expressed in other tissues, including, uterus, trachea, lung, stomach, esophagus, immune cells, and spinal cord (Mastrangeli et al, 2003;Moriwaki et al, 2007Moriwaki et al, , 2009). Thus, SLURPs as well as ACh can regulate lymphocyte function via AChR-mediated pathways (Moriwaki et al, 2007).…”

Section: Positive Allosteric Modulatorsmentioning

confidence: 99%

Positive and negative modulation of nicotinic receptors

Arias

2010

Advances in Protein Chemistry and Structural Biology

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Section: Positive Allosteric Modulatorsmentioning

confidence: 99%

Positive and negative modulation of nicotinic receptors

Arias

2010

Advances in Protein Chemistry and Structural Biology

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“…SLURP1 is expressed abundantly in the cornea and moderately in oral mucosa, skin and other epithelia, where it is secreted into tear, saliva, sweat, and urine (Adermann et al, 1999; Norman et al, 2004). It is also expressed in bronchial epithelial cells, a variety of immune cells, primary sensory neurons, and the retina (Fujii et al, 2014; Horiguchi et al, 2009; Mastrangeli et al, 2003; Matsumoto et al, 2012; Moriwaki et al, 2007, 2009). SLURP1 is a ligand of α7-nAchR and a late marker of epidermal differentiation (Chimienti et al, 2003; Favre et al, 2007; Horiguchi et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HUVEC tube formation via suppression of NFκB suggests an anti-angiogenic role for SLURP1 in the transparent cornea

Loughner

Swamynathan

2017

Experimental Eye Research

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Previously, we have reported that the Secreted Ly6/uPAR related protein-1 (SLURP1) serves an important immunomodulatory function in the ocular surface. Here, we examine the involvement of SLURP1 in regulating corneal angiogenic privilege. Slurp1 expression detected by QPCR, immunoblots and immunofluorescent stain, was significantly decreased in mouse corneas subjected to alkali burn-induced corneal neovascularization (CNV). Addition of exogenous SLURP1 (6XHis-tagged, E. coli expressed and partially purified using Ni-ion columns) significantly suppressed the tumor necrosis factor-α (TNF-α)- stimulated human umbilical cord vascular endothelial cell (HUVEC) tube formation. SLURP1 suppressed the HUVEC tube length, tube area and number of branch points, without affecting their viability and/or proliferation. Exogenous SLURP1 in HUVEC also suppressed the TNF-α-induced (i) interleukin-8 (IL-8) and TNF-α production, (ii) adhesion to different components of the extracellular matrix, (iii) migration, and (iv) nuclear localization of NFκB. Together, these results demonstrate that SLURP1 suppresses HUVEC tube formation by blocking nuclear translocation of NFκB, and suggest a potential role for SLURP1 in promoting corneal angiogenic privilege.

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“…3 (1)(2)(3)(4)(5)(6)(7)(8). In the central nervous system, LYNX1 and LYNX2 regulate nAChR activity, preventing excessive excitation (3,4).…”

mentioning

confidence: 99%

“…LYNX1 knock-out mice demonstrated enhanced performance in specific tests of learning ability and memory, whereas loss of LYNX2 results in increased anxiety-related behaviors (3,4). Prototoxins have also been shown to affect cell growth in lung carcinoma (9), are involved in skin diseases (6,7), and are related to prostate stem cell antigen (10).…”

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confidence: 99%

NMR Structure and Action on Nicotinic Acetylcholine Receptors of Water-soluble Domain of Human LYNX1

Lyukmanova

Шенкарев

Shulepko

et al. 2011

Journal of Biological Chemistry

132

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Discovery of proteins expressed in the central nervous system sharing the three-finger structure with snake ␣-neurotoxins provoked much interest to their role in brain functions. Prototoxin LYNX1, having homology both to Ly6 proteins and threefinger neurotoxins, is the first identified member of this family membrane-tethered by a GPI anchor, which considerably complicates in vitro studies. We report for the first time the NMR spatial structure for the water-soluble domain of human LYNX1 lacking a GPI anchor (ws-LYNX1) and its concentration-dependent activity on nicotinic acetylcholine receptors (nAChRs). At 5-30 M, ws-LYNX1 competed with 125 I-␣-bungarotoxin for binding to the acetylcholine-binding proteins (AChBPs) and to Torpedo nAChR. Exposure of Xenopus oocytes expressing ␣7 nAChRs to 1 M ws-LYNX1 enhanced the response to acetylcholine, but no effect was detected on ␣4␤2 and ␣3␤2 nAChRs. Increasing ws-LYNX1 concentration to 10 M caused a modest inhibition of these three nAChR subtypes. A common feature for ws-LYNX1 and LYNX1 is a decrease of nAChR sensitivity to high concentrations of acetylcholine. NMR and functional analysis both demonstrate that ws-LYNX1 is an appropriate model to shed light on the mechanism of LYNX1 action. Computer modeling, based on ws-LYNX1 NMR structure and AChBP x-ray structure, revealed a possible mode of ws-LYNX1 binding.Endogenous "prototoxins" like LYNX1, LYNX2, SLURP-1, and SLURP-2, belonging to the Ly6 protein family, modulate nicotinic acetylcholine receptors (nAChRs) 3 (1-8). In the central nervous system, LYNX1 and LYNX2 regulate nAChR activity, preventing excessive excitation (3, 4). Gene deletion of LYNX1 or LYNX2 indicates that these modulators are critical for nAChR function in the brain. LYNX1 knock-out mice demonstrated enhanced performance in specific tests of learning ability and memory, whereas loss of LYNX2 results in increased anxiety-related behaviors (3, 4). Prototoxins have also been shown to affect cell growth in lung carcinoma (9), are involved in skin diseases (6, 7), and are related to prostate stem cell antigen (10).LYNX1 and LYNX2 are tethered to the membrane by a GPI anchor, which considerably complicates in vitro studies. LYNX1 is co-localized in the brain with ␣4␤2 and ␣7 nAChRs (1-3), and its modulatory activity on ␣4␤2 nAChR was shown in experiments on Xenopus oocytes (1, 3). It was reported that soluble form of LYNX1 (not containing a GPI anchor) potentiates ␣4␤2 receptor (1), but the concentration at which it acts remains unknown. A secreted water-soluble protein SLURP-1 expressed in palmoplantar skin acts on ␣7 nAChR and regulates keratinocyte proliferation (5).It was predicted that the prototoxins should have a spatial structure similar to that of snake venom ␣-neurotoxins, effective competitive inhibitors of nAChR (1). ␣-Neurotoxins are characterized by a three-finger fold formed by three adjacent loops arising from a small globular hydrophobic core, crosslinked by four conserved disulfide bonds (11-13). Nicotinic acetylcholine receptors are ta...

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Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand

Cited by 58 publications

References 36 publications

Positive and negative modulation of nicotinic receptors

Positive and negative modulation of nicotinic receptors

Inhibition of HUVEC tube formation via suppression of NFκB suggests an anti-angiogenic role for SLURP1 in the transparent cornea

NMR Structure and Action on Nicotinic Acetylcholine Receptors of Water-soluble Domain of Human LYNX1

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