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Molecular Regulation of Lysophosphatidic Acid Receptor 1 Maturation and Desensitization

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Abstract

Lysophosphatidic acid receptor 1 (LPA1) belongs to the G protein-coupled receptor family. The ligand for LPA1 is LPA, the simplest lysophospholipid. LPA is considered a growth factor and induces cell proliferation, anti-apoptosis, and cell migration. The pro-inflammatory and pro-fibrotic roles of LPA have also been well-demonstrated. Most of the biological functions of LPA are mostly executed through LPA1. The mature form of LPA1 is glycosylated and localized on the plasma membrane. LPA1 is bound to heterotrimetric G proteins and transduces intracellular signaling in response to ligation to LPA. Desensitization of LPA1 negatively regulates LPA1-mediated signaling and the resulting biological functions. Phosphorylation and ubiquitination are well-demonstrated posttranslational modifications of GPCR. In this review, we will discuss our knowledge of LPA1 glycosylation, maturation, and trafficking from the endoplasmic reticulum (ER)/Golgi to the plasma membrane. Moreover, in light of recent findings, we will also discuss molecular regulation of LPA1 internalization and stability.

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Abbreviations

LPA:

lysophosphatidic acid

GPCR:

G protein-coupled receptor

ER:

endoplasmic reticulum

ERK:

extracellular signal-regulated kinase

PI3K:

phosphatidylinositol-3-kinase

COPII:

coat protein complex II

SNPs:

single nucleotide polymorphisms

GRK2:

GPCR kinase 2

EGFR:

epidermal growth factor receptor

TrkA:

tropomyosin receptor kinase A

ERAD:

ER-associated degradation

PKC:

protein kinase C

FFA4:

free fatty acid receptor 4

PMA:

phorbol ester

LPS:

lipopolysaccharide

PROTACs:

proteolysis-targeting chimeras.

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Acknowledgements

This work was supported by grants from National Institutes of Health (R01HL131665, R01HL157164, HL136294 to Y.Z., R01 GM115389, R01HL151513 to J.Z.).

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  1. Department of Physiology and Cell Biology, the Ohio State University, Columbus, OH, USA

    Jing Zhao, Thomas Stephens & Yutong Zhao

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  1. Jing Zhao
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  2. Thomas Stephens
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  3. Yutong Zhao
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Correspondence to Yutong Zhao.

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Zhao, J., Stephens, T. & Zhao, Y. Molecular Regulation of Lysophosphatidic Acid Receptor 1 Maturation and Desensitization. Cell Biochem Biophys 79, 477–483 (2021). https://doi.org/10.1007/s12013-021-00999-6

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