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GPR162 is a beta cell CART receptor

Lindqvist, Andreas LU ; Abels, Mia LU ; Shcherbina, Liliya LU ; Ngara, Mtakai LU orcid ; Kryvokhyzha, Dmytro LU ; Chriett, Sabrina LU ; Riva, Matteo LU ; Fajul, Abul ; Barghouth, Mohammad LU and Luan, Cheng LU , et al. (2023) In iScience 26(12).
Abstract

Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion.... (More)

Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.

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@article{df4cff20-bcba-49a8-abc5-c89908ee29bc,
  abstract     = {{<p>Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.</p>}},
  author       = {{Lindqvist, Andreas and Abels, Mia and Shcherbina, Liliya and Ngara, Mtakai and Kryvokhyzha, Dmytro and Chriett, Sabrina and Riva, Matteo and Fajul, Abul and Barghouth, Mohammad and Luan, Cheng and Eliasson, Lena and Larsen, Olav and Rosenkilde, Mette M. and Zhang, Enming and Renström, Erik and Wierup, Nils}},
  issn         = {{2589-0042}},
  keywords     = {{Biological sciences; Endocrinology; Natural sciences; Physiology}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{GPR162 is a beta cell CART receptor}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2023.108416}},
  doi          = {{10.1016/j.isci.2023.108416}},
  volume       = {{26}},
  year         = {{2023}},
}