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.
Highlights
As a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily, acid-sensing ion channel 1a (ASIC1a) senses pH changes and has an extensive distribution pattern and function in the peripheral tissues and central nervous system (Radu et al, 2016)
IL-1β and tumor necrosis factor-α (TNF-α) play a role in ASIC1a protein synthesis through the NF-κB signaling pathway in the following ways (Zhou et al, 2018): (1) Co-expression of ASIC1a and NF-κB p65 was high in articular cartilage tissues, especially in adjuvant arthritis (AA) rats, an experimental animal model of rheumatoid arthritis (RA); (2) IL-1β or TNF-α increased the translocation of NF-κB p65 to the nucleus in a time-dependent manner; (3) IL-1β- or TNFα-induced ASIC1a expression was partially abrogated by pyrrolidine dithiocarbamate (PDTC); (4) IL-1β or TNF-α enhanced the activity of the ASIC1a gene promoter by increasing the DNA-binding activities of NF-κB, which could be inhibited by PDTC. These results demonstrate that NF-κB activation is involved in the synthesis of the ASIC1a protein induced by IL-1β or TNF-α
Recent studies have demonstrated that ASIC1a plays a crucial role in the occurrence and development of diseases related to the central and peripheral nervous system, and it is considered to be a potential therapeutic target
Summary
As a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily, acid-sensing ion channel 1a (ASIC1a) senses pH changes and has an extensive distribution pattern and function in the peripheral tissues and central nervous system (Radu et al, 2016). Several studies have demonstrated that protein synthesis, degradation, and membrane trafficking of ASIC1a are affected by various factors.
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