دورية أكاديمية
AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2.
العنوان: | AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2. |
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المؤلفون: | Frachon N; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.; CNRS, ERL8228, F-75006 Paris, France., Demaretz S; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.; CNRS, ERL8228, F-75006 Paris, France., Seaayfan E; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.; CNRS, ERL8228, F-75006 Paris, France., Chelbi L; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.; CNRS, ERL8228, F-75006 Paris, France., Bakhos-Douaihy D; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.; CNRS, ERL8228, F-75006 Paris, France., Laghmani K; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.; CNRS, ERL8228, F-75006 Paris, France. |
المصدر: | Cells [Cells] 2024 Feb 24; Vol. 13 (5). Date of Electronic Publication: 2024 Feb 24. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
مواضيع طبية MeSH: | Endoplasmic Reticulum-Associated Degradation* , Bartter Syndrome*/genetics , Bartter Syndrome*/metabolism, Female ; Pregnancy ; Humans ; Endoplasmic Reticulum/metabolism ; Ubiquitination ; Membrane Proteins/metabolism ; Solute Carrier Family 12, Member 1 |
مستخلص: | Inactivating mutations of kidney Na-K-2Cl cotransporter NKCC2 lead to antenatal Bartter syndrome (BS) type 1, a life-threatening salt-losing tubulopathy. We previously reported that this serious inherited renal disease is linked to the endoplasmic reticulum-associated degradation (ERAD) pathway. The purpose of this work is to characterize further the ERAD machinery of NKCC2. Here, we report the identification of ancient ubiquitous protein 1 (AUP1) as a novel interactor of NKCC2 ER-resident form in renal cells. AUP1 is also an interactor of the ER lectin OS9, a key player in the ERAD of NKCC2. Similar to OS9, AUP1 co-expression decreased the amount of total NKCC2 protein by enhancing the ER retention and associated protein degradation of the cotransporter. Blocking the ERAD pathway with the proteasome inhibitor MG132 or the α-mannosidase inhibitor kifunensine fully abolished the AUP1 effect on NKCC2. Importantly, AUP1 knock-down or inhibition by overexpressing its dominant negative form strikingly decreased NKCC2 polyubiquitination and increased the protein level of the cotransporter. Interestingly, AUP1 co-expression produced a more profound impact on NKCC2 folding mutants. Moreover, AUP1 also interacted with the related kidney cotransporter NCC and downregulated its expression, strongly indicating that AUP1 is a common regulator of sodium-dependent chloride cotransporters. In conclusion, our data reveal the presence of an AUP1-mediated pathway enhancing the polyubiquitination and ERAD of NKCC2. The characterization and selective regulation of specific ERAD constituents of NKCC2 and its pathogenic mutants could open new avenues in the therapeutic strategies for type 1 BS treatment. |
References: | Methods Mol Biol. 2012;832:455-61. (PMID: 22350905) Biol Cell. 2018 Sep;110(9):205-216. (PMID: 29989181) News Physiol Sci. 2000 Dec;15:309-312. (PMID: 11390932) Nat Rev Nephrol. 2017 Dec;13(12):721. (PMID: 28989176) J Biol Chem. 2017 Aug 4;292(31):12813-12827. (PMID: 28630040) Comput Struct Biotechnol J. 2023 Sep 09;21:4478-4487. (PMID: 37736299) EMBO Rep. 2018 May;19(5):. (PMID: 29519897) Am J Physiol Regul Integr Comp Physiol. 2005 Apr;288(4):R782-95. (PMID: 15793031) Biol Cell. 2012 Nov;104(11):658-76. (PMID: 22708623) Kidney Int. 2006 Jan;69(2):304-12. (PMID: 16408120) Int J Mol Sci. 2022 Oct 23;23(21):. (PMID: 36361553) J Biol Chem. 2011 Mar 18;286(11):9489-502. (PMID: 21205824) J Biol Chem. 2005 May 13;280(19):19419-25. (PMID: 15760896) Curr Opin Nephrol Hypertens. 2015 Mar;24(2):111-6. (PMID: 25602517) Curr Opin Cell Biol. 2011 Aug;23(4):483-91. (PMID: 21571517) Int J Mol Sci. 2021 Feb 23;22(4):. (PMID: 33672238) Am J Hum Genet. 1998 Jun;62(6):1332-40. (PMID: 9585600) PLoS Biol. 2021 Dec 8;19(12):e3001474. (PMID: 34879065) Cells. 2021 Dec 29;11(1):. (PMID: 35011665) Mol Cell. 2019 Jan 17;73(2):377-389.e11. (PMID: 30581143) Hypertension. 2004 Feb;43(2):341-6. (PMID: 14718354) Cell Death Dis. 2023 Jul 27;14(7):473. (PMID: 37500613) J Biol Chem. 2008 Jun 13;283(24):16446-54. (PMID: 18417469) Biochem J. 2007 Jun 15;404(3):353-63. (PMID: 17521290) Physiol Rev. 2012 Apr;92(2):537-76. (PMID: 22535891) J Biol Chem. 2000 Dec 29;275(52):40757-64. (PMID: 10984471) Biol Cell. 2012 Apr;104(4):201-12. (PMID: 22211456) Mol Immunol. 2009 Feb;46(4):505-15. (PMID: 18952287) Mol Biol Cell. 2009 Sep;20(18):4059-69. (PMID: 19625452) J Biol Chem. 2002 Aug 9;277(32):28934-41. (PMID: 12042322) J Mol Biol. 2009 Jan 30;385(4):1032-42. (PMID: 19084021) Clin J Am Soc Nephrol. 2018 Feb 7;13(2):242-250. (PMID: 29146702) J Cell Biol. 2019 Oct 7;218(10):3171-3187. (PMID: 31537714) Physiol Rev. 2005 Apr;85(2):423-93. (PMID: 15788703) Hum Genet. 2013 Feb;132(2):179-87. (PMID: 23104236) J Biol Chem. 2011 Oct 28;286(43):37602-14. (PMID: 21857022) Nat Med. 2013 Dec;19(12):1655-60. (PMID: 24185693) J Biol Chem. 2011 Jan 14;286(2):1292-300. (PMID: 21062743) FEBS J. 2006 Apr;273(7):1331-49. (PMID: 16689923) Mol Biol Cell. 2018 Jun 15;29(12):1422-1434. (PMID: 29688814) Front Physiol. 2012 Jul 16;3:263. (PMID: 22934019) Trends Biochem Sci. 2018 Aug;43(8):593-605. (PMID: 30056836) J Lipid Res. 2013 Feb;54(2):503-13. (PMID: 23197321) Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12325-30. (PMID: 18711132) J Cell Biol. 2014 Mar 17;204(6):869-79. (PMID: 24637321) Nat Genet. 1996 Jun;13(2):183-8. (PMID: 8640224) J Biol Chem. 2011 Feb 18;286(7):5599-606. (PMID: 21127063) Curr Pharm Des. 2013;19(19):3497-508. (PMID: 23331027) J Biol Chem. 2016 Feb 26;291(9):4487-502. (PMID: 26721884) J Biol Chem. 2011 Dec 16;286(50):43454-64. (PMID: 22006919) Clin Investig. 1994 Sep;72(9):692-4. (PMID: 7849450) J Biol Chem. 2002 Sep 13;277(37):34413-23. (PMID: 12093806) N Engl J Med. 2016 May 12;374(19):1853-63. (PMID: 27120771) Front Physiol. 2022 Sep 07;13:971251. (PMID: 36160843) J Biol Chem. 2007 Nov 16;282(46):33817-33830. (PMID: 17848580) PLoS One. 2017 Apr 6;12(4):e0173924. (PMID: 28384259) Am J Physiol. 1996 Nov;271(5 Pt 2):F961-6. (PMID: 8945989) Curr Protein Pept Sci. 2019;20(12):1226-1245. (PMID: 31187709) Cell Stress Chaperones. 1996 Jun;1(2):117-25. (PMID: 9222597) Hum Mutat. 2021 Aug;42(8):947-968. (PMID: 33973684) Annu Rev Physiol. 2002;64:803-43. (PMID: 11826289) J Biol Chem. 2010 Jul 2;285(27):20732-9. (PMID: 20435896) Annu Rev Pathol. 2015;10:173-94. (PMID: 25387057) Platelets. 2009 Mar;20(2):105-10. (PMID: 19235052) |
معلومات مُعتمدة: | ANR-17-CE14-0040 -Pheno2Geno Agence Nationale de la Recherche |
فهرسة مساهمة: | Keywords: AUP1; Bartter syndrome; CKD; ER quality control; ERAD; ion transport; kidney |
المشرفين على المادة: | 0 (AUP1 protein, human) 0 (Membrane Proteins) 0 (Solute Carrier Family 12, Member 1) |
SCR Disease Name: | Bartter syndrome, antenatal type 1 |
تواريخ الأحداث: | Date Created: 20240313 Date Completed: 20240314 Latest Revision: 20240315 |
رمز التحديث: | 20240315 |
مُعرف محوري في PubMed: | PMC10931229 |
DOI: | 10.3390/cells13050389 |
PMID: | 38474353 |
قاعدة البيانات: | MEDLINE |
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