Analyzing the Signaling Properties of Gar (Lepisosteus oculatus) Melanocortin Receptors: Evaluating Interactions with MRAP1 and MRAP5

Publication Date

7-2-2019

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Biological Sciences

Keywords

ACTH, Evolution, Lepisosteus oculatus, Melanocortin receptors, α-MSH

Abstract

RT-PCR analysis of gar pituitary and brain indicated that different combinations of gar melanocortin receptor mRNAs are present in the same tissues with mRNAs for gar mrap1 and gar mrap2. Against this background, an objective of this study was to determine whether the ligand sensitivity for either ACTH or α-MSH was affected when gar (g) melanocortin receptors (Mcrs) were co-expressed with either of the accessory proteins gMrap1 or gMrap2 in Chinese Hamster Ovary cells. The results indicated that gMc2r has an obligatory requirement for co-expression with gMrap1 in order for the receptor to be activated by hACTH(1-24). In addition, activation of gMc2r did not occur when the receptor was expressed alone or co-expressed with gMrap2. Furthermore, co-expression of gMc2r with gMrap1 followed by stimulation with NDP-MSH resulted in a low level of activation (only at 10-7 M and 10-6 M). However, gMc1r, gMc3r, gMc4r, and gMc5r responded to stimulation by NDP-MSH in a more robust manner. Co-expression of gMc1r, gMc3r, gMc4r, and gMc5r with gMRAP1 had no effect on sensitivity to stimulation by NDP-MSH or hACTH(1-24). Co-expression with gMRAP2 had no negative or positive effect on ligand sensitivity for gMc1r, gMc3r, and gMc5r, however this treatment did increase the activation of CHO cells transfected with gMc4r following stimulation with both hACTH(1-24) (p < 0.001), and NDP-MSH (p < 0.001). Co-expression of gMC5R with either gMRAP1 or gMRAP2 increased trafficking of gMC5R to the plasma membrane. These pharmacological observations are compared to the response of melanocortin receptors from other neopterygian fishes, cartilaginous fishes, and tetrapods to stimulation by ACTH(1-24) and forms of α-MSH.

Copyright Date

7-2-2019

Copyright Statement / License for Reuse

All Rights Reserved
All Rights Reserved.

Rights Holder

Elsevier Inc.

Provenance

Received from author

Language

English (eng)

Extent

10 pgs

Publication Statement

Copyright is held by Elsevier Inc. User is responsible for all copyright compliance.

Publication Title

General and Comparative Endocrinology

Volume

282

First Page

1

Last Page

10

ISSN

1095-6840

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