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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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type
Contribution to journal
publication status
published
subject
keywords
Biological sciences, Endocrinology, Natural sciences, Physiology
in
iScience
volume
26
issue
12
article number
108416
publisher
Elsevier
external identifiers
  • pmid:38077141
  • scopus:85177871704
ISSN
2589-0042
DOI
10.1016/j.isci.2023.108416
language
English
LU publication?
yes
id
df4cff20-bcba-49a8-abc5-c89908ee29bc
date added to LUP
2023-12-20 14:45:21
date last changed
2024-11-15 22:34:38
@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}},
}