SLC9 Gene Family: Function, Expression, and Regulation

Abstract

The Slc9 family of Na /H exchangers (NHEs) plays a critical role in electroneutral exchange of Na and H in the mammalian intestine as well as other absorptive and secretory epithelia of digestive organs. These transport proteins contribute to the transepithelial Na and water absorption, intracellular pH and cellular volume regulation as well as the electrolyte, acid-base, and fluid volume homeostasis at the systemic level. They also influence the function of other membrane transport mechanisms, affect cellular proliferation and apoptosis as well as cell migration, adherence to the extracellular matrix, and tissue repair. Additionally, they modulate the extracellular milieu to facilitate other nutrient absorption and to regulate the intestinal microbial microenvironment. Na /H exchange is inhibited in selected gastrointestinal diseases, either by intrinsic factors (e.g., bile acids, inflammatory mediators) or infectious agents and associated bacterial toxins. Disrupted NHE activity may contribute not only to local and systemic electrolyte imbalance but also to the disease severity via multiple mechanisms. In this review, we describe the cation proton antiporter superfamily of Na /H exchangers with a particular emphasis on the eight SLC9A isoforms found in the digestive tract, followed by a more integrative description in their roles in each of the digestive organs. We discuss regulatory mechanisms that determine the function of Na /H exchangers as pertinent to the digestive tract, their regulation in pathological states of the digestive organs, and reciprocally, the contribution of dysregulated Na /H exchange to the disease pathogenesis and progression. © 2018 American Physiological Society. Compr Physiol 8:555-583, 2018.

A guide to plasma membrane solute carrier proteins

“…SLC9A1 is expressed in almost every tissue in the body, although the transporter is often localized to specialized membrane domains in tissues [297,298]. Other SLC9 transporters are expressed in a more tissue or temporally dependent manner, like SLC9A4, which is expressed primarily in the stomach [292]. Cellular localization of these proteins varies greatly within the family as well, with SLC9A1, SLC9A2, and SLC9A4 (NHE4) all localizing to the plasma membrane of cells [289].…”

FengLiao affects gut microbiota and the expression levels of Na+/H+ exchangers, aquaporins and acute phase proteins in mice with castor oil-induced diarrhea

“…Studies have shown that aquaporins (AQPs) [17][18][19] and Na+/H+ exchangers (NHEs) [20][21][22][23][24] are critical for the absorptive and secretory function of the gastric epithelia. In addition, serum levels of acute phase proteins (APPs) [25,26] are correlated with the severity of diarrhea and intestinal inflammation.…”

Transcriptional network analysis of transcriptomic diversity in resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system

“…Two further zinc transporters, Slc39a2 and Slc39a11, were enriched in lung macrophages (Cluster 10). This lung macrophage-enriched cluster also contains Slc52a3, encoding a riboflavin transporter, Slc6a4 (sodium and chloride dependent sodium symporter) and 2 members of the Slc9 family of sodium-hydrogen exchange (NHE) transporters (Slc9a4 and Slc9a7) which are more traditionally associated with epithelial function [149].…”