Evaluation of Hydroxycarboxylic Acid Receptor 1 (HCAR1) as a Building Block for Genetically Encoded Extracellular Lactate Biosensors.
Details
Serval ID
serval:BIB_6DA16749D2D1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evaluation of Hydroxycarboxylic Acid Receptor 1 (HCAR1) as a Building Block for Genetically Encoded Extracellular Lactate Biosensors.
Journal
Biosensors
ISSN
2079-6374 (Electronic)
ISSN-L
2079-6374
Publication state
Published
Issued date
25/02/2022
Peer-reviewed
Oui
Volume
12
Number
3
Pages
142
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
The status of lactate has evolved from being considered a waste product of cellular metabolism to a useful metabolic substrate and, more recently, to a signaling molecule. The fluctuations of lactate levels within biological tissues, in particular in the interstitial space, are crucial to assess with high spatial and temporal resolution, and this is best achieved using cellular imaging approaches. In this study, we evaluated the suitability of the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1, formerly named GPR81), as a basis for the development of a genetically encoded fluorescent lactate biosensor. We used a biosensor strategy that was successfully applied to molecules such as dopamine, serotonin, and norepinephrine, based on their respective G-protein-coupled receptors. In this study, a set of intensiometric sensors was constructed and expressed in living cells. They showed selective expression at the plasma membrane and responded to physiological concentrations of lactate. However, these sensors lost the original ability of HCAR1 to selectively respond to lactate versus other related small carboxylic acid molecules. Therefore, while representing a promising building block for a lactate biosensor, HCAR1 was found to be sensitive to perturbations of its structure, affecting its ability to distinguish between related carboxylic molecules.
Keywords
Biosensing Techniques, Lactic Acid/metabolism, Receptors, G-Protein-Coupled/metabolism, Signal Transduction, GPR81, HCAR1, circularly permuted green fluorescent protein, genetically encoded fluorescent indicator, lactate
Pubmed
Web of science
Open Access
Yes
Create date
11/04/2022 9:48
Last modification date
08/08/2024 7:25