Syndecans modulate ghrelin receptor signaling.

Area of Science:

• Cellular and Molecular Biology
• Endocrinology
• Metabolism Research

Background:

• Ghrelin, a gut hormone, stimulates appetite and growth hormone secretion via the GHSR.
• Syndecans (SDCs) are membrane proteins involved in hypothalamic appetite signaling.
• Previous research indicated ghrelin interacts with SDCs.

Purpose of the Study:

• To investigate how SDCs modulate ghrelin signaling at the GHSR.
• To assess the impact of SDCs on ghrelin-induced intracellular calcium (iCa2+) mobilization and inositol phosphate 1 (IP1) production.
• To explore the downstream signaling pathways affected by SDCs in ghrelin signaling.

Main Methods:

• HEK293 cells were used to assess ghrelin-induced iCa2+ mobilization and IP1 production.
• Overexpression of SDCs and GNAQ/11 knockout cells were utilized.
• Ghrelin-stimulated Gαq activation and β-arrestin2 recruitment were measured.

Main Results:

• SDC overexpression dose-dependently increased maximum iCa2+ and IP1 responses to ghrelin.
• SDCs reduced constitutive GHSR activity and plasma membrane GHSR levels.
• SDCs significantly reduced ghrelin-induced β-arrestin2 recruitment, with a delayed peak response.

Conclusions:

• SDCs enhance ghrelin-induced iCa2+ and IP1 signaling at GHSR, potentially by modulating downstream pathways of Gαq.
• SDCs reduce β-arrestin2 recruitment to GHSR in response to ghrelin.
• This SDC-mediated modulation of ghrelin signaling may represent a novel mechanism affecting metabolism and obesity.