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  Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells

Grunddal, K. V., Tonack, S., Egerod, K. L., Thompson, J. J., Petersen, N., Engelstoft, M. S., et al. (2021). Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells. MOLECULAR METABOLISM, 51: 101231. doi:10.1016/j.molmet.2021.101231.

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Grunddal, Kaare V., Author
Tonack, Sarah1, Author              
Egerod, Kristoffer L., Author
Thompson, Jonathan James, Author
Petersen, Natalia, Author
Engelstoft, Maja S., Author
Vagne, Constance, Author
Keinse, Celine, Author
Gradwohl, Gerard, Author
Offermanns, Stefan1, Author              
Schwartz, Thue W., Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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Free keywords: CHAIN FATTY-ACIDS; BRUSH CELLS; G-PROTEIN; GUT MICROBIOTA; STEM-CELLS; CHEMOSENSORY CELLS; MUCOSAL IMMUNITY; TYPE-2 IMMUNITY; IN-VITRO; L-DOPAEndocrinology & Metabolism; ADGRG2; GPR64; GPCRs; Tuft cells; Chemosensory cells;
 Abstract: Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract. Methods: Transgenic Gpr64mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft cells was confirmed by specific cell ablation. The GPCR repertoire of intestinal Gpr64mCherry-positive tuft cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64mCherry was crossed into the general tuft cell reporter Trpm5GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNAseq analysis. Results: Expression of the Gpr64mCherry reporter was identified in multiple organs and specifically in olfactory microvillous cells, enteric nerves, and importantly in respiratory and GI tuft cells. In the small intestine, cell ablation targeting Gpr64-expressing epithelial cells eliminated tuft cells. Transcriptional analysis of small intestinal Gpr64mCherry -positive tuft cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5GFP:Gpr64mCherry mice revealed sequential expression of initially Trpm5GFP and subsequently also Gpr64mCherry in maturing intestinal tuft cells. RNA-seq analysis of small intestinal tuft cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft cells. Conclusions: GPR64 is expressed in chemosensory epithelial cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft cells. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Language(s): eng - English
 Dates: 2021-04-052021-09
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
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Title: MOLECULAR METABOLISM
Source Genre: Journal
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Publ. Info: RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS : ELSEVIER
Pages: - Volume / Issue: 51 Sequence Number: 101231 Start / End Page: - Identifier: ISSN: 2212-8778