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Review
. 2020 Oct 23:8:596304.
doi: 10.3389/fcell.2020.596304. eCollection 2020.

Factors and Molecular Mechanisms Influencing the Protein Synthesis, Degradation and Membrane Trafficking of ASIC1a

Yayun Xu  1   2   3 , Feihu Chen  1   2   3
Affiliations
Review

Factors and Molecular Mechanisms Influencing the Protein Synthesis, Degradation and Membrane Trafficking of ASIC1a

Yayun Xu et al. Front Cell Dev Biol. .

Abstract

Acid-sensing ion channels (ASICs) are members of the degenerin/epithelial sodium channel superfamily. They are extracellular pH sensors that are activated by protons. Among all ASICs, ASIC1a is one of the most intensively studied isoforms because of its unique ability to be permeable to Ca2+. In addition, it is considered to contribute to various pathophysiological conditions. As a membrane proton receptor, the number of ASIC1a present on the cell surface determines its physiological and pathological functions, and this number partially depends on protein synthesis, degradation, and membrane trafficking processes. Recently, several studies have shown that various factors affect these processes. Therefore, this review elucidated the major factors and underlying molecular mechanisms affecting ASIC1a protein expression and membrane trafficking.

Keywords: acid-sensing ion channel 1a; factors; membrane trafficking; molecular mechanisms; protein expression.

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Figures

FIGURE 1
FIGURE 1
A schematic representation of the underlying molecular mechanisms influencing the protein synthesis, degradation, and dynamic trafficking processes of ASIC1a. The NF-κB pathway: inflammatory cytokines including IL-6, IL-1β, TNF-α, and NGF and their receptor interactions activate the NF-κB pathways, leading to the translocation of NF-κB p65 into the nucleus and enhancing the ASIC1a gene promoter activity, thereby upregulating ASIC1a expression; The PI3K/Akt pathway: BDNF/TrkB or PDGF activates the intracellular PI3K/Akt pathway, and then, induces ASIC1a phosphorylation in vesicle and forward targeting to the plasma membrane; The endocytic pathway: downregulation of ASIC1a surface expression in a clathrin- and dynamin-dependent endocytosis; Autophagy-lysosome pathway: β-estradiol/ERα or acute ethanol exposure enhances ASIC1a protein degradation via the autophagy-lysosome pathway.
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