Related Experiment Video

Updated: Jun 19, 2025

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
12:37

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

18.2K

Melanocortin-4 Receptor PLC Activation Is Modulated by an Interaction with the Monocarboxylate Transporter 8

Larissa Anthofer1,2, Philipp Gmach1, Zeynep Cansu Uretmen Kagiali1

  • 1Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, D-10117 Berlin, Germany.

International Journal of Molecular Sciences
|July 27, 2024
PubMed

Insights

Monocarboxylate transporter 8 (MCT8) interacts with the melanocortin-4 receptor (MC4R) in the hypothalamus. This interaction modulates MC4R signaling, suggesting MCT8 has a broader role in G protein-coupled receptor modulation.

Area of Science:

  • Neuroendocrinology
  • Molecular Endocrinology
  • GPCR Signaling

Background:

  • The melanocortin-4 receptor (MC4R) is crucial for regulating appetite and energy balance via the hypothalamic leptin pathway.
  • G protein-coupled receptors (GPCRs), including MC4R, can form heterodimers with other membrane proteins, influencing their function.
  • Thyroid hormones (TH) are vital for energy homeostasis, and their transport is mediated by monocarboxylate transporter 8 (MCT8), which also interacts with GPCRs.

Purpose of the Study:

  • To investigate a potential interaction between MC4R and MCT8 in hypothalamic neurons.
  • To elucidate the functional consequences of this MC4R-MCT8 interplay on receptor signaling.

Main Methods:

  • Single-cell RNA-sequencing data analysis to confirm co-expression of MC4R and MCT8 in hypothalamic neurons.
  • Development of a novel fluorescent staining protocol to demonstrate co-localization of MC4R and MCT8 in human brain tissue.
  • In vitro assays including Bioluminescence Resonance Energy Transfer (BRET), inositol phosphate 1 (IP1) accumulation, and cyclic adenosine monophosphate (cAMP) determination.

Main Results:

  • MC4R and MCT8 were found to co-localize in human brain tissue.
  • MCT8 was shown to modulate MC4R-mediated phospholipase C activation through a direct interaction.
  • This modulation of MC4R signaling by MCT8 did not affect cAMP formation and did not require a functional MCT8 transporter.

Conclusions:

  • MCT8 exhibits an extended functional role as a modulator of GPCR signaling, specifically impacting MC4R activity.
  • The findings support the investigation of further GPCR interactions with proteins possessing underrepresented physiological functions.
  • This study highlights a novel mechanism in energy homeostasis regulation involving MC4R and MCT8.
Keywords:
BRETMC4RMCT8fluorophore-labeled ligandheterodimerizationprotein–protein interaction

More Related Videos

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays08:27

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays

Published on: October 20, 2023

1.6K
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.4K

Related Concept Videos

Cholinergic Receptors: Muscarinic01:25

Cholinergic Receptors: Muscarinic

The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
2.1K
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
319
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
24.7K
Cholinergic Antagonists: Pharmacokinetics01:24

Cholinergic Antagonists: Pharmacokinetics

Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations,  while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
426
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists01:23

Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
236
Transcellular Transport of Solutes01:23

Transcellular Transport of Solutes

Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
3.5K