Polycystin-2 is regulated by endoplasmic reticulum-associated degradation

Human Molecular Genetics
Genqing LiangXing-Zhen Chen

Abstract

Endoplasmic reticulum(ER)-associated degradation (ERAD) is an essential process for cell homeostasis and remains not well understood. During ERAD, misfolded proteins are recognized, ubiquitinated on ER and subsequently retro-translocated/dislocated from ER to the 26S proteasome in the cytosol for proteolytic elimination. Polycystin-2 (PC2), a member of the transient receptor potential superfamily of cation channels, is a Ca channel mainly located on ER and primary cilium membranes of cells. Mutations in PC2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The cellular and molecular mechanisms underlying the PC2-associated pathogenesis remain unclear. Here we show that PC2 degradation is regulated by the ERAD pathway through the ubiquitin-proteasome system. PC2 interacted with ATPase p97, a well-known ERAD component extracting substrates from ER, and immobilized it in perinuclear regions. PC2 also interacted with Herp, an ubiquitin-like protein implicated in regulation of ERAD. We found that Herp is required for and promotes PC2 degradation. ER stress accelerates the retro-translocation of PC2 for cytosolic degradation, at least in part through increasing the Herp expression. Thus, PC2 is a novel ERAD su...Continue Reading

Citations

Jun 11, 2009·Antioxidants & Redox Signaling·Jeffrey G Dickhout, Joan C Krepinsky
Aug 10, 2010·Nephron. Experimental Nephrology·Stephen B MasonVincent H Gattone
Jan 31, 2014·Molecular Biology of the Cell·Julia LeitmanGerardo Z Lederkremer
Aug 28, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Carlo SpirliMario Strazzabosco
May 21, 2009·Kidney International·Vicente E Torres, Peter C Harris
Jul 23, 2015·Kidney International·Albert C M Ong, Peter C Harris
May 24, 2011·Biochimica Et Biophysica Acta·Toshihiro MarutaniHiroto Komano
Mar 28, 2008·Experimental Cell Research·Arnaud F KleinBernard Brais
Aug 30, 2008·The FEBS Journal·Xing-Zhen ChenHoracio F Cantiello
Jan 25, 2014·The Journal of Biological Chemistry·Valeriu CebotaruWilliam B Guggino
May 21, 2010·Critical Reviews in Biochemistry and Molecular Biology·Youngah Jo, Russell A Debose-Boyd
May 1, 2019·Nature Reviews. Nephrology·Catherine Meyer-Schwesinger
Jan 24, 2019·Cold Spring Harbor Perspectives in Biology·Patrick G NeedhamJeffrey L Brodsky
Apr 2, 2014·The Journal of Physiology·Kevin Retailleau, Fabrice Duprat
Aug 30, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jungwoo YangXing-Zhen Chen
Jul 4, 2009·Annual Review of Physiology·Jing Zhou
Feb 1, 2020·Scientific Reports·Wendy A LeaChristopher J Ward
Sep 12, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Connie P C OwRoger G Evans
Apr 11, 2014·The Journal of Biological Chemistry·Alexis HofherrMichael Köttgen
Oct 19, 2017·Scientific Reports·Natalia TorrealbaSergio Lavandero
Feb 21, 2021·Cell Death & Disease·Po-Han ChenJen-Tsan Chi
Jun 19, 2019·Biochimie·Asma BoukhalfaNicolas Dupont
Sep 7, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qin YaoValeriu Cebotaru

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