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GPR162 is a beta cell CART receptor
Andreas Lindqvist1, Mia Abels1, Liliya Shcherbina1
1Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden.
Iscience
|December 11, 2023
Summary
Cocaine and amphetamine-regulated transcript (CART) signaling in pancreatic beta cells is mediated by G protein-coupled receptor 162 (GPR162). This study identifies GPR162 as the CART receptor, crucial for insulin secretion and cytoskeletal regulation.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Cocaine and amphetamine-regulated transcript (CART) is known to influence insulin secretion in pancreatic islets.
- The specific receptor for CART in pancreatic beta cells has remained unidentified.
- Previous work established insulinotropic actions of CART in human and rodent islets.
Purpose of the Study:
- To identify the receptor mediating CART's effects in pancreatic beta cells.
- To investigate the role of G protein-coupled receptor 162 (GPR162) in CART signaling.
- To elucidate the mechanisms by which CART influences insulin secretion and cellular function.
Main Methods:
- RNA sequencing of Cartpt knockdown INS-1 832/13 cells to identify potential receptors.
- Binding assays including proximity ligation assay, radioactive binding, and co-immunoprecipitation to confirm CART-GPR162 interaction.
- Gpr162 knockdown experiments to assess the functional impact on CART-mediated effects.
- Analysis of insulin secretion and cytoskeletal arrangement in response to CART stimulation.
Main Results:
- GPR162 was identified as the most Cartpt-regulated receptor via RNA sequencing.
- CART binding to GPR162 was confirmed using multiple biochemical and proximity assays.
- Gpr162 knockdown resulted in reduced CART binding, blunted CART-induced exocytosis, and decreased insulin secretion.
- A novel GPR162-dependent role for CART in regulating cytoskeletal arrangement was discovered.
Conclusions:
- G protein-coupled receptor 162 (GPR162) is identified as the functional receptor for Cocaine and amphetamine-regulated transcript (CART) in pancreatic beta cells.
- GPR162 mediates CART's effects on insulin secretion, exocytosis, and cytoskeletal organization.
- These findings provide crucial mechanistic insights into CART-regulated beta cell function.
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