ArticleThe Journal of biological chemistry2010
BetaPix up-regulates Na+/H+ exchanger 3 through a Shank2-mediated protein-protein interaction.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Targeted intestinal deletion of Rho guanine nucleotide exchange factor 7, βPIX, impairs enterocyte proliferation, villus maturation, and mucosal defenses in mice.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Article
- Pathophysiology of Intestinal NaCellular and molecular gastroenterology and hepatology · 2017Article
- Shank2 Regulates Renal Albumin Endocytosis.Physiological reports · 2015Article
- Serum- and glucocorticoid-induced protein kinase 1 (SGK1) increases the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells by phosphorylating Shank2E protein.The Journal of biological chemistry · 2014Article
- Shank2 mutant mice display a hypersecretory response to cholera toxin.The Journal of physiology · 2014Article
- Na⁺/H⁺ exchanger regulatory factor 3 is critical for multidrug resistance protein 4-mediated drug efflux in the kidney.Journal of the American Society of Nephrology : JASN · 2014Article
- Shank2 contributes to the apical retention and intracellular redistribution of NaPiIIa in OK cells.American journal of physiology. Cell physiology · 2013Article
- Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion.Physiological reviews · 2012Review
- Role of βPix in the Kidney.Frontiers in physiology · 2012Article
- SLC9/NHE gene family, a plasma membrane and organellar family of Na⁺/H⁺ exchangers.Molecular aspects of medicineReview
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Na(+)/H(+) exchanger 3 (NHE3) plays an important role in neutral Na(+) transport in mammalian epithelial cells. The Rho family of small GTPases and the PDZ (PSD-95/discs large/ZO-1) domain-based adaptor Shank2 are known to regulate the membrane expression and activity of NHE3. In this study we examined the role of betaPix, a guanine nucleotide exchange factor for the Rho GTPase and a strong binding partner to Shank2, in NHE3 regulation using integrated molecular and physiological approaches. Immunoprecipitation and pulldown assays revealed that NHE3, Shank2, and betaPix form a macromolecular complex when expressed heterologously in mammalian cells as well as endogenously in rat colon, kidney, and pancreas. In addition, these proteins co-segregated at the apical surface of rat colonic epithelial cells, as detected by immunofluorescence staining. When expressed in PS120/NHE3 cells, betaPix increased membrane expression and basal activity of NHE3. Interestingly, the effects of betaPix on NHE3 were abolished by cotransfection with dominant-negative Shank2 mutants and by treatment with Clostridium difficile toxin B, a Rho GTPase inhibitor, indicating that Shank2 and Rho GTPases are involved in betaPix-mediated NHE3 regulation. Knockdown of endogenous betaPix by RNA interference decreased Shank2-induced increase of NHE3 membrane expression in HEK 293T cells. These results indicate that betaPix up-regulates NHE3 membrane expression and activity by Shank2-mediated protein-protein interaction and by activating Rho GTPases in the apical regions of epithelial cells.
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