دورية أكاديمية
Functional characterization of melanocortin 2 receptor (Mc2r) from a lobe-finned fish (Protopterus annectens) and insights into the molecular evolution of melanocortin receptors.
| العنوان: | Functional characterization of melanocortin 2 receptor (Mc2r) from a lobe-finned fish (Protopterus annectens) and insights into the molecular evolution of melanocortin receptors. |
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| المؤلفون: | Shaughnessy CA; Department of Biological Sciences, University of Denver, Denver, CO, USA. Electronic address: Ciaran.Shaughnessy@DU.edu., Le K; Department of Biological Sciences, University of Denver, Denver, CO, USA., Myhre VD; Department of Biological Sciences, University of Denver, Denver, CO, USA., Dores RM; Department of Biological Sciences, University of Denver, Denver, CO, USA. |
| المصدر: | General and comparative endocrinology [Gen Comp Endocrinol] 2023 Nov 01; Vol. 343, pp. 114356. Date of Electronic Publication: 2023 Aug 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0370735 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6840 (Electronic) Linking ISSN: 00166480 NLM ISO Abbreviation: Gen Comp Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | alpha-MSH* , Receptor, Melanocortin, Type 2*/genetics , Receptor, Melanocortin, Type 2*/metabolism, Animals ; Humans ; Adrenocorticotropic Hormone/pharmacology ; Alanine/genetics ; Evolution, Molecular ; Mammals/metabolism ; Receptors, Melanocortin/genetics ; Receptors, Melanocortin/metabolism ; Zebrafish/genetics ; Zebrafish/metabolism |
| مستخلص: | Recent studies from our group on melanocortin 2 receptors (Mc2r) from basal families of actinopterygians have served to resolve that Mrap1 dependence and ACTH selectivity are features of even the most basal ray-finned fishes. However, there have been no studies on Mc2r function of the basal sarcopterygians, the lobe-finned fishes, represented by the extant members coelacanths and lungfishes. Here, we offer the first molecular and functional characterization of an Mc2r from a lobe-finned fish, the West African lungfish (Protopterus annectens). Plasmids containing cDNA constructs of lungfish (lf) Mc2r and Mrap1 were expressed in mammalian and zebrafish cell lines. Cells were then stimulated by human ACTH(1-24) and melanocyte stimulating hormone (α-MSH), as well as alanine-substituted analogs of hACTH(1-24) targeting residues within the H 6 F 7 R 8 W 9 and K 15 K 16 R 17 R 18 P 19 motifs. Activation of lfMc2r was assessed using a cAMP-responsive luciferase reporter gene assay. In these assays, lfMc2r required co-expression with lfMrap1, was selective for ACTH over α-MSH at physiological concentrations of the ligands, and was completely inhibited by multiple-alanine substitutions of the HFRW (A 6-9 ) and KKRRP (A 15-19 ) motifs. Single- and partial-alanine substitutions of the HFRW and KKRRP motifs varied in their impacts on receptor-ligand affinity from having no effect to completely inhibiting lfMc2r activation. This characterization of the Mc2r of a lobe-finned fish fulfills the last major extant vertebrate group for which Mc2r function had yet to be characterized. In doing so, we resolve that all basal bony vertebrate groups exhibit Mc2r function that substantially differs from that of the cartilaginous fishes, indicating that rapid and dramatic shift in Mc2r function occurred between the radiation of cartilaginous fishes and the emergence of bony fishes. We support this interpretation with a molecular clock analysis of the melanocortin receptors, which demonstrates the uniquely high rate of sequence divergence in Mc2r. Much remains to be understood regarding the molecular evolution of Mc2r during the early radiation of vertebrates that resulted in the derived functional characteristics of Mrap1 dependence and exclusive selectivity for ACTH. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ACTH; Lungfish; Mc2r; Molecular evolution; Mrap |
| المشرفين على المادة: | 9002-60-2 (Adrenocorticotropic Hormone) OF5P57N2ZX (Alanine) 581-05-5 (alpha-MSH) 0 (Receptor, Melanocortin, Type 2) 0 (Receptors, Melanocortin) |
| تواريخ الأحداث: | Date Created: 20230810 Date Completed: 20230923 Latest Revision: 20230923 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.ygcen.2023.114356 |
| PMID: | 37562700 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1095-6840 |
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| DOI: | 10.1016/j.ygcen.2023.114356 |