Article
Cell Biology
Xiaolu Tai, Song Xue, Cong Zhang, Yu Liu, Jie Chen, Yu Han, Gufa Lin, Chao Zhang
Summary: Melanocortin-3 receptor (MC3R) and Melanocortin-4 receptor (MC4R), crucial for energy balance in vertebrates, are modulated by Melanocortin accessory proteins (MRAPs). In Xenopus tropicalis, MRAPs play a role in fine-tuning the pharmacological activities of neuronal MC3R and MC4R signaling, converting them into ACTH-preferred receptors. This control over receptor activity is relevant to the complex transition of feeding behaviors in their life history.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Xiaozhu Wang, Song Xue, Xiaowei Lei, Wenqi Song, Lei Li, Xuan Li, Yanbin Fu, Cong Zhang, Hailin Zhang, Yao Luo, Meng Wang, Gufa Lin, Chao Zhang, Jing Guo
Summary: In this study, the researchers investigated the role of MRAP2 in the regulation of central melanocortin signaling in the Mexican axolotl. They found that the conservation of axolotl mc3r and mc4r is higher than mrap2, and the axolotl MC3R/MC4R is closer to their counterparts in the clawed frog. The researchers also confirmed the co-expression and functional complex formation of axolotl MC3R/MC4R and MRAP2 on the plasma membrane.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yang Zhou, Monica K. Chawla, Jose L. Rios-Monterrosa, Lingzhi Wang, Marc A. Zempare, Victor J. Hruby, Carol A. Barnes, Minying Cai
Summary: The study found significant correlations between the expression of MCR subtypes in the frontal cortex/hypothalamus and hippocampus regions and the performance of spatial learning and memory in aged rats, supporting the hypothesis that aging has a direct impact on MCR expression and function.
Article
Cell Biology
Meng Wang, Yue Zhai, Liumei Lu, Cong Zhang, Na Li, Song Xue, Daofu Cheng, Shaliu Fu, Qi Liu, Chao Zhang
Summary: This study revealed the bidirectional homo- and hetero-dimeric topologies of two zebrafish MRAP2 isoforms on the plasma membrane, investigated their regulatory roles on MC4R signaling, and identified the carboxyl terminal as the functional domain.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Cell Biology
Lei Li, Ying Xu, Jihong Zheng, Zhe Kuang, Cong Zhang, Na Li, Gufa Lin, Chao Zhang
Summary: The study revealed a specific regulatory pattern of the melanocortin system in Xenopus laevis, where MRAP2 proteins directly interact with MC4R proteins on the cell surface in a functional antiparallel dimeric topology.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mutaz Amin, Jurg Ott, Rongling Wu, Teodor T. Postolache, Claudia Gragnoli
Summary: Melanocortin receptor genes are associated with the risk of major depressive disorder (MDD) and type 2 diabetes (T2D). This study found that MC2R and MC5R genes are associated with MDD, while MC1R, MC2R, MC3R, and MC4R genes are associated with T2D. These findings provide important insights into the role of melanocortin receptor genes in the comorbidity of MDD and T2D.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Meng Wang, Linyu Pi, Xiaowei Lei, Lei Li, Jing Xu, Zhe Kuang, Cong Zhang, Liang Li, Chao Zhang
Summary: The study modified the structure of MRAP2 and generated six distinct conformational variants, demonstrating the importance of the orientation of each domain for MRAP2 function and its regulatory effects on MC4R.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Marty Kwok-Shing Wong, Robert M. Dores
Summary: RT-PCR analysis showed that steroidogenic tissues are distributed along the length of the kidney in the spotted gar. The expression of mc2r and mc5r mRNA in the kidney suggests different responses to ACTH stimulation. Phylogenetic and selection pressure analyses indicated that the mc2r and mc5r genes are evolving at different rates after duplication.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Li-Qin Ji, Ying-Zhu Rao, Yong Zhang, Rong Chen, Ya-Xiong Tao
Summary: In this study, the orange-spotted grouper's Mc5r gene was cloned and its pharmacological characteristics were investigated. Four ligands were found to bind to Mc5r, increasing intracellular cAMP levels. Mrap2 was found to regulate the surface expression and activity of Mc5r. This study provides new insights into the pharmacology and regulation of fish Mc5r.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Ting Liu, Ti-Lin Yi, Dai-Qin Yang, Ya-Xiong Tao
Summary: The study found that maMC5R can bind to three agonists and induce intracellular cAMP production. Compared with hMC5R, maMC5R showed decreased maximal binding but higher binding affinity, with significantly lower EC50 and maximal response when stimulated with alpha-MSH or ACTH (1-24). MaMRAP2s had no effect on cell surface expression of maMC5R, but significantly increased maximal binding.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2021)
Article
Biology
Jing Xu, Meng Wang, Yanbin Fu, Cong Zhang, Zhe Kuang, Shan Bian, Rui Wan, Shen Qu, Chao Zhang
Summary: By reversing the wild-type MRAP2 protein sequences, researchers created novel functional modulators for regulating MC4R signaling. The reversed MRAP2 proteins demonstrated proper topology and interaction with MC4R signaling in mice and zebrafish. These findings provide important insights for the development of therapeutic drugs for MC4R-related disorders.
Article
Endocrinology & Metabolism
Rachel Forfar, Mashal Hussain, Puneet Khurana, Jennifer Cook, Steve Lewis, Dillon Popat, David Jackson, Ed McIver, Jeff Jerman, Debra Taylor, Adrian J. L. Clark, Li F. Chan
Summary: The overproduction of ACTH leads to significant morbidity, but there is currently no effective medical treatment to directly block its action. This study identified a highly specific MC2R antagonist, providing a foundation for the clinical investigation of small-molecule ACTH antagonists as therapeutic agents.
ENDOCRINE CONNECTIONS
(2022)
Article
Endocrinology & Metabolism
Ciaran A. Shaughnessy, Khoa Le, Valorie D. Myhre, Robert M. Dores
Summary: Recent studies show that even the most basic ray-finned fishes have features of Mrap1 dependence and ACTH selectivity. However, there have been no studies on Mc2r function in lobe-finned fishes. This article provides the first molecular and functional characterization of Mc2r from a lobe-finned fish, the West African lungfish, demonstrating its selective response to ACTH.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hui-Xia Yu, Yang Li, De-Bin Zhong, Xin Ren, Hao-Lin Mo, Ze-Bin Jiang, Jia-Jia Yu, Dong-Mei Xiong, Hai-Xia Liu, Li-Xin Wang
Summary: This study discovered that MRAP2a protein in rainbow trout interacts with MC3R and MC4R proteins and is involved in regulating their basal activity and signaling. The findings are significant for understanding the conserved role of MC4R and MC3R signaling in teleost fish growth and energy homeostasis, especially in cold-water fish.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Review
Physiology
Francesca Copperi, Jung Dae Kim, Sabrina Diano
Summary: The melanocortin system plays a crucial role not only in regulating energy homeostasis, food intake, and glucose levels, but also in modulating cardiovascular functions such as blood pressure and heart rate. Its effects are exerted through central and peripheral mechanisms involving receptors MC3R and MC4R, influencing sympathetic nervous activity and potentially improving cardiovascular outcomes in diseases like myocardial and cerebral ischemia. This review discusses the central regulation of the melanocortin system in essential cardiovascular functions and its protective role in ischemic events.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Cell Biology
Karina A. Pena, Sofya Savransky, Breanna Lewis
Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu
Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu
Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou
Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin
Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera
Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban
Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen
Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)