SLC9A3R2

Last update 08 May 2025

Basic Info

Synonyms

E3KARP, Na(+)/H(+) exchange regulatory cofactor NHE-RF2, NHE3 kinase A regulatory protein E3KARP

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Introduction

Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus.

100 Clinical Results associated with SLC9A3R2

100 Translational Medicine associated with SLC9A3R2

0 Patents (Medical) associated with SLC9A3R2

222

Literatures (Medical) associated with SLC9A3R2

01 Jun 2025·Archives of Medical Research

NHERF2 regulatory function in signal transduction pathways and control of gene expression: Implications for cellular homeostasis and breast cancer

Review

Author: Aguilar-Arce, Isaac Esaú ; Paredes-Villa, Adrián-Alejandro ; Valadéz-Graham, Viviana ; Meneses-Morales, Iván ; Cervantes-Roldán, Rafael ; León-Del-Río, Alfonso

Na⁺/H⁺ exchanger regulatory factor 2 (NHERF2) is a nucleocytoplasmic protein initially identified as a regulator of membrane-bound sodium-hydrogen exchanger 3 (NHE3). In the cytoplasm, NHERF2 regulates the activity of G protein-coupled receptors (GPCRs), including beta-2 adrenergic receptor (2β-AR), lysophosphatidic acid receptor 2, and parathyroid hormone type 1 receptor. In the nucleus, NHERF2 acts as a coregulator of transcription factors such as sex-determining region Y protein (SRY), involved in male sex determination, and estrogen receptor alpha (ERα). ERα is a ligand-dependent transcription factor that controls mammary gland growth and differentiation during puberty and pregnancy and plays a major role in the development and progression of breast cancer tumors. Altogether, the regulatory functions of NHERF2 on ion channels, GPCRs, and nuclear transcription factors have a modulatory effect on signal transduction pathways, metabolic homeostasis, cell proliferation and differentiation, neurotransmission, muscle contraction, and renal electrolyte balance. This work highlights NHERF2 functions in the cytoplasm and nucleus and underscores the nuclear mechanisms through which NHERF2 participates in the regulation of gene expression and tumor growth and progression in breast cancer.

01 Dec 2024·Theriogenology

Sirtuin 1-mediated autophagy regulates testosterone synthesis in Leydig cells of piglets

Article

Author: Abouelfetouh, Mahmoud M ; Yu, Lingyun ; He, Yijing ; Ju, Shiqiang ; Li, Qiao ; Zhang, Yanyan ; Zhou, Zhenlei ; Abouelfetouh, Mahmoud M. ; Liu, Chengyin

Testosterone is secreted by Leydig cells (LCs), which play an important physiological role in preserving male secondary sex characteristics, protecting male reproductive function, and establishing the blood-testis barrier. Studies have shown that autophagy is particularly active in LCs; however, its involvement in testosterone synthesis in porcine LCs has not been fully explored. Therefore, this experiment aimed to investigate the influence of autophagy on testosterone secretion in porcine LCs and its potential regulatory mechanism. Our results demonstrated that both testicular autophagy and serum testosterone levels increased in piglets during postnatal development from 4 to 18 weeks. In addition, autophagy was found to degrade the Na⁺/H⁺ exchange regulatory factor 2 (NHERF2), leading to the up-regulation of scavenger receptor class B type 1 (SRB1). This process resulted in increased cholesterol intake and enhanced testosterone production. The observable level of sirtuin 1 (SIRT1) was directly proportional to the level of autophagy. In vitro investigations have shown that SIRT1 can affect the level of autophagy, cholesterol uptake as well as testosterone release. In conclusion, testosterone synthesis during pig development is regulated by SIRT1. SIRT1 mediates the degradation of NHERF2 through autophagy, thereby weakening its negative regulatory effect on the high-density lipoprotein receptor SRB1 in Leydig cells. This process increases cholesterol uptake and enhances testosterone synthesis.

01 Apr 2024·Acta Physiologica

cGMP‐dependent kinase 2, Na⁺/H⁺ exchanger NHE3, and PDZ‐adaptor NHERF2 co‐assemble in apical membrane microdomains

Article

Author: Liu, Yongjian ; Nikolovska, Katerina ; Riederer, Brigitte ; Luo, Min ; Patrucco, Enrico ; Seidler, Ursula ; Hofmann, Franz

AbstractAimTrafficking, membrane retention, and signal‐specific regulation of the Na+/H+ exchanger 3 (NHE3) are modulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ‐adapter proteins. This study explored the assembly of NHE3 and NHERF2 with the cGMP‐dependent kinase II (cGKII) within detergent‐resistant membrane microdomains (DRMs, “lipid rafts”) during in vivo guanylate cycle C receptor (Gucy2c) activation in murine small intestine.MethodsSmall intestinal brush border membranes (siBBMs) were isolated from wild type, NHE3‐deficient, cGMP‐kinase II‐deficient, and NHERF2‐deficient mice, after oral application of the heat‐stable Escherichia coli toxin (STa) analog linaclotide. Lipid raft and non‐raft fractions were separated by Optiprep density gradient centrifugation of Triton X‐solubilized siBBMs. Confocal microscopy was performed to study NHE3 redistribution after linaclotide application in vivo.ResultsIn the WT siBBM, NHE3, NHERF2, and cGKII were strongly raft associated. The raft association of NHE3, but not of cGKII, was NHERF2 dependent. After linaclotide application to WT mice, lipid raft association of NHE3 decreased, that of cGKII increased, while that of NHERF2 did not change. NHE3 expression in the BBM shifted from a microvillar to a terminal web region. The linaclotide‐induced decrease in NHE3 raft association and in microvillar abundance was abolished in cGKII‐deficient mice, and strongly reduced in NHERF2‐deficient mice.ConclusionNHE3, cGKII, and NHERF2 form a lipid raft‐associated signal complex in the siBBM, which mediates the inhibition of salt and water absorption by Gucy2c activation. NHERF2 enhances the raft association of NHE3, which is essential for its close interaction with the exclusively raft‐associated activated cGKII.

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SLC9A3R2

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