Function
Sodium-hydrogen exchange regulatory factors (NHERF) or ezrin-radixin-moesin binding phosphoprotein-50 or PDZ domain-containing protein or Na+/H+ exchange regulatory cofactor NHE-RF1 or NHERF are multifunctional adaptor protein which plays a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin skeleton[1].
- NHERF-1 is the major isoform present in the brain and it regulates the trans-cellular ion transport through the blood-brain barrier membrane[2]. It transduces cyclic AMP signals that inhibit the sodium-hydrogen exchanger present at the surface of kidney and gut[3]. NHERF-1 contains 2 PDZ domains and one erm domain.
- NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling[4]. NHERF-2 contains 2 PDZ domains and one erm domain.
- NHERF-3 contains 4 PDZ domains no erm domain[5].
Relevance
NHERF-1 inhibitors represent a potentially effective therapeutic approach to the treatment of hear failure[6]. NHERF-1 has a vital role in kidney cell survival[7]. NHERF are known to be involved in pathophysiologies of many brain diseases like epilepsy, Alzhheimer's disease, neuropathic pain and stroke.
Structural highlights
NHERF interacts with ion transporters and receptors via its PDZ domains and with the merlin, ezrin, radixin and moesin proteins via its c-terminal. The CXCR2 peptide binds the second PDZ domain hydrophobic cleft[8].
3D Structures of sodium-hydrogen exchange regulatory factor
Sodium-hydrogen exchange regulatory factor 3D structures
References
- ↑ Stemmer-Rachamimov AO, Wiederhold T, Nielsen GP, James M, Pinney-Michalowski D, Roy JE, Cohen WA, Ramesh V, Louis DN. NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas. Am J Pathol. 2001 Jan;158(1):57-62. doi: 10.1016/S0002-9440(10)63944-2. PMID:11141479 doi:http://dx.doi.org/10.1016/S0002-9440(10)63944-2
- ↑ Song S, Sun X, Li X, Yuan Y, Jiao N. Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization. Org Lett. 2015 Jun 19;17(12):2886-9. doi: 10.1021/acs.orglett.5b00932. Epub 2015 , May 26. PMID:26010555 doi:http://dx.doi.org/10.1021/acs.orglett.5b00932
- ↑ Weinman EJ, Steplock D, Shenolikar S. NHERF-1 uniquely transduces the cAMP signals that inhibit sodium-hydrogen exchange in mouse renal apical membranes. FEBS Lett. 2003 Feb 11;536(1-3):141-4. PMID:12586353 doi:10.1016/s0014-5793(03)00043-7
- ↑ Bhattacharya R, Wang E, Dutta SK, Vohra PK, E G, Prakash YS, Mukhopadhyay D. NHERF-2 maintains endothelial homeostasis. Blood. 2012 May 17;119(20):4798-806. PMID:22343917 doi:10.1182/blood-2011-11-392563
- ↑ Donowitz M, Cha B, Zachos NC, Brett CL, Sharma A, Tse CM, Li X. NHERF family and NHE3 regulation. J Physiol. 2005 Aug 15;567(Pt 1):3-11. PMID:15905209 doi:10.1113/jphysiol.2005.090399
- ↑ Morris K. Targeting the myocardial sodium-hydrogen exchange for treatment of heart failure. Expert Opin Ther Targets. 2002 Jun;6(3):291-8. doi: 10.1517/14728222.6.3.291 . PMID:12223070 doi:http://dx.doi.org/10.1517/14728222.6.3.291
- ↑ Parker MD, Myers EJ, Schelling JR. Na+-H+ exchanger-1 (NHE1) regulation in kidney proximal tubule. Cell Mol Life Sci. 2015 Jun;72(11):2061-74. doi: 10.1007/s00018-015-1848-8. Epub , 2015 Feb 14. PMID:25680790 doi:http://dx.doi.org/10.1007/s00018-015-1848-8
- ↑ Song S, Sun X, Li X, Yuan Y, Jiao N. Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization. Org Lett. 2015 Jun 19;17(12):2886-9. doi: 10.1021/acs.orglett.5b00932. Epub 2015 , May 26. PMID:26010555 doi:http://dx.doi.org/10.1021/acs.orglett.5b00932
