Melanin-concentrating hormone receptor 1 is discarded by exosomes after internalization

Area of Science:

• Cell biology
• Neuroendocrinology
• G protein-coupled receptor signaling

Background:

• Melanin-concentrating hormone receptor 1 (MCHR1) is a G protein-coupled receptor involved in appetite and metabolism.
• MCHR1 signaling is initiated by MCH binding and leads to calcium signaling, followed by receptor internalization.
• The fate of MCHR1 after internalization is not well understood.

Purpose of the Study:

• To investigate the extracellular fate of MCHR1 following ligand-induced internalization.
• To determine if MCHR1 is secreted from cells and the mechanism of this secretion.

Main Methods:

• Cell culture and stimulation with MCH ligand.
• Analysis of MCHR1 localization and trafficking using microscopy and biochemical assays.
• Exosome isolation and characterization.
• Functional assays to assess MCHR1 activity in recipient cells.

Main Results:

• MCHR1 is secreted extracellularly via exosomes following MCH stimulation and internalization.
• A specific, highly glycosylated form of MCHR1 is selectively recruited to exosomes.
• Truncation of MCHR1 at the C-terminus prevents both MCH response and exosomal recruitment.
• MCHR1 transferred to other cells via exosomes does not exhibit functionality.

Conclusions:

• MCHR1 can be secreted via exosomes, suggesting a novel pathway for receptor regulation.
• Exosomal secretion of MCHR1 may serve as a mechanism to terminate intracellular signaling.
• This process could have implications for understanding MCHR1's role in physiological and pathological conditions.