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An enhanced TRPC3 activity is related to adverse effects, including pathological hypertrophy in chronic cardiac disease states. In the present study, we identified FK506-binding protein 52 (FKBP52, also known as FKBP4) as a novel interaction partner of TRPC3 in the heart. FKBP52 was recovered from a cardiac cDNA library by a C-terminal TRPC3 fragment (amino acids 742\u2013848) in a yeast two-hybrid screen. Downregulation of FKBP52 promoted a TRPC3-dependent hypertrophic response in neonatal rat cardiomyocytes (NRCs). A similar effect was achieved by overexpressing peptidyl-prolyl isomerase (PPIase)-deficient FKBP52 mutants. Mechanistically, expression of the FKBP52 truncation mutants elevated TRPC3-mediated currents and Ca2+ fluxes, and the activation of calcineurin and the nuclear factor of activated T-cells in NRCs. Our data demonstrate that FKBP52 associates with TRPC3 via an as-yet-undescribed binding site in the C-terminus of TRPC3 and modulates TRPC3-dependent Ca2+ signals in a PPIase-dependent manner. This functional interaction might be crucial for limiting TRPC3-dependent signaling during chronic hypertrophic stimulation.<\/jats:p>","DOI":"10.1242\/jcs.231506","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T12:55:12Z","timestamp":1568984112000},"source":"Crossref","is-referenced-by-count":16,"title":["FKBP52 regulates TRPC3-dependent Ca2+ signals and the hypertrophic growth of cardiomyocyte cultures"],"prefix":"10.1242","volume":"132","author":[{"given":"Sandra","family":"Bandleon","sequence":"first","affiliation":[{"name":"Comprehensive Heart Failure Center Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"},{"name":"University Hospital Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick P.","family":"Strunz","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"},{"name":"University Hospital Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Pickel","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Wuerzburg 2 , R\u00f6ntgenring 9, 97070 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandra","family":"Tiapko","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz 3 , 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cellini","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"},{"name":"University Hospital Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Miranda-Laferte","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Wuerzburg 2 , R\u00f6ntgenring 9, 97070 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6072-8963","authenticated-orcid":false,"given":"Petra","family":"Eder-Negrin","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"},{"name":"University Hospital Wuerzburg 1 , The Department of Internal Medicine I , , Am Schwarzenberg 15, 97078 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"2024061318361218700_JCS231506C1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1385\/1-59259-671-1:251","article-title":"Ras signaling pathway for analysis of protein-protein interactions in yeast and mammalian cells","volume":"250","author":"Aronheim","year":"2004","journal-title":"Methods Mol. 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