Functional role of <i>N</i>‐linked glycosylation on the rat melanin‐concentrating hormone receptor 1

Saito, Yumiko; Tetsuka, Mitsue; Li, Yue; Kawamura, Yuuki; Maruyama, Kei

doi:10.1016/s0014-5793(02)03744-4

Cited by 36 publications

(27 citation statements)

References 28 publications

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“…Sphyrna MCH-R1 and MCH-R2 contain potential DRY motif in intracellular loop 2, N-glycosylation sites in its amino terminus and phosphorylation sites in its carboxyl terminus. Those motif and amino acid residues are found to be essential for MCH function in rat [1,35,36], and well conserved in teleosts [27,41]. The present study revealed that these genes are expressed in the brain of S. lewini, suggesting that both receptor subtypes are responsible for the central role of MCH in S. lewini.…”

Section: Discussionsupporting

confidence: 57%

Identification of mRNAs coding for mammalian-type melanin-concentrating hormone and its receptors in the scalloped hammerhead shark Sphyrna lewini

Mizusawa¹,

Amiya²,

Yamaguchi³

et al. 2012

General and Comparative Endocrinology

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Section: Discussionsupporting

confidence: 57%

Identification of mRNAs coding for mammalian-type melanin-concentrating hormone and its receptors in the scalloped hammerhead shark Sphyrna lewini

Mizusawa¹,

Amiya²,

Yamaguchi³

et al. 2012

General and Comparative Endocrinology

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“…For these reasons, the two specific LHCGR polymorphisms Asn291Ser (rs12470652) and Ser312Asn (rs2293275) located in exon 10 are good candidate markers for association studies. Moreover, they are located near to glycosylation sites potentially increasing the possibility to affect LH or hCG action, since glycosylation plays an important role in the GPCR family for signalling regulation and physiological features of the receptor trafficking regulation [198]. However, no association between Asn291Ser or Ser312Asn and breast cancer was found in a large cohort of Dutch patients compared to healthy controls, although in vitro transfection studies revealed increased receptor sensitivity for the Ser291/Asn312 haplotype due to an altered glycosylation status [199].…”

Section: Role Of the Exon 10 Of Lhcgr In Breast Cancermentioning

confidence: 99%

Effects of polymorphisms in gonadotropin and gonadotropin receptor genes on reproductive function

Casarini

Pignatti

Simoni

2011

Rev Endocr Metab Disord

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Gonadotropins, the action of which is mediated at the level of their gonadal receptors, play a key role in sexual development, reproductive functions and in metabolism. The involvement of the gonadotropins and their receptor genotypes on reproductive function are widely studied. A large number of gonadotropins and their receptors gene polymorphisms are known, but the only one considerable as a clear, absolute genetic marker of reproductive features or disfunctions is the FSHR Asn680Ser polymorphism, since it modulates ovarian response to FSH. The aim of these studies would to be the prediction of the genetic causes of sex-related diseases to enable a customized clinical setting based on individual response of patients undergoing gonadotropin stimulation. In this review we discuss the latest information about the effects of polymorphisms of the gonadotropins and their receptor genes on reproductive functions of both male and female, and discuss their patho-physiological implications.

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“…To determine whether the rescue of MCHR1-T 255 A by NBI-A was widely applicable to other mutations of the receptor, we set out to measure what effect NBI-A treatment had on the cell surface expression of several other mutants that show poor trafficking to the cell surface (22)(23)(24). We selected three mutant receptors from recently published work based on their reported reduced cell surface expression and evidence that the mutant receptor was localized to the perinuclear zone of the cytoplasm.…”

Section: Nbi-a Can Rescue Other Mchr1 Mutantsmentioning

confidence: 99%

A Point Mutation in the Human Melanin Concentrating Hormone Receptor 1 Reveals an Important Domain for Cellular Trafficking

Fan

Perry

Gao

et al. 2005

Molecular Endocrinology

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G protein-coupled receptors (GPCRs) are heptahelical integral membrane proteins that require cell surface expression to elicit their effects. The lack of appropriate expression of GPCRs may be the underlying cause of a number of inherited disorders. There is evidence that newly synthesized GPCRs must attain a specific conformation for their correct trafficking to the cell surface. In this study, we show that a single point mutation in human melanin-concentrating hormone receptor (hMCHR1) at position 255 (T255A), which is located at the junction of intracellular loop 3 and transmembrane domain 6, reduces the hMCHR1 cell surface expression level to 20% of that observed for the wild-type receptor. Most of these mutant receptors are located intracellularly, as opposed to the wild-type receptor, which is located primarily on the cell surface. Immunoprecipitation experiments show that hMCHR1-T255A has reduced glycosylation compared with the wild-type receptor and is associated with the chaperone protein, calnexin, and it colocalizes in the endoplasmic reticulum with KDEL-containing proteins. We also demonstrate that a cell-permeable small molecule antagonist of hMCHR1 can function as a pharmacological chaperone to restore cell surface expression of this and other MCHR1 mutants to wild-type levels. Once rescued, the T255A mutant couples to Gq proteins as efficiently as the wild-type receptor. These data suggest that this single mutation produces an hMCHR1 that folds incorrectly, resulting in its retention in the endoplasmic reticulum, but once rescued to the cell surface can still function normally.

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Functional role of N‐linked glycosylation on the rat melanin‐concentrating hormone receptor 1

Cited by 36 publications

References 28 publications

Identification of mRNAs coding for mammalian-type melanin-concentrating hormone and its receptors in the scalloped hammerhead shark Sphyrna lewini

Identification of mRNAs coding for mammalian-type melanin-concentrating hormone and its receptors in the scalloped hammerhead shark Sphyrna lewini

Effects of polymorphisms in gonadotropin and gonadotropin receptor genes on reproductive function

A Point Mutation in the Human Melanin Concentrating Hormone Receptor 1 Reveals an Important Domain for Cellular Trafficking

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