The Transient receptor potential (TRP; C-classical; TRPC) channel TRPC3 permeates a cation (Na+/Ca2+) influx that is favoured by the stimulation of Gq protein-coupled receptors (GPCRs). 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) 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 742-848) in a yeast two-hybrid screen. Downregulation of FKBP52 promoted a TRPC3-dependent hypertrophic response in neonatal rat cardiomyocytes (NRC). A similar effect was achieved by overexpressing PPIase-deficient FKBP52 mutants. Mechanistically, FKBP52 truncated mutants elevated TRPC3-mediated currents and Ca2+ fluxes, 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.
FKBP52 regulates TRPC3-dependent Ca2+ signals and the hypertrophic growth of cardiomyocyte cultures
Currently Viewing Accepted Manuscript - Newer Version Available
Sandra Bandleon, Patrick P. Strunz, Simone Pickel, Oleksandra Tiapko, Antonella Cellini, Erick Miranda-Laferte, Petra Eder-Negrin; FKBP52 regulates TRPC3-dependent Ca2+ signals and the hypertrophic growth of cardiomyocyte cultures. J Cell Sci 2019; jcs.231506. doi: https://doi.org/10.1242/jcs.231506
Download citation file:
Advertisement
Imaging Cell Architecture and Dynamics
We are still welcoming submissions for our upcoming Special Issue: Imaging Cell Architecture and Dynamics. This issue will be coordinated by two Guest Editors: Lucy Collinson (The Francis Crick Institute, UK) and Guillaume Jacquemet (University of Turku, Finland). Extended submission deadline: 29 March 2024.
Journal of Cell Science - more than just a journal
People who know JCS well will know that we're more than just a journal and that our community – the cell biology community – really is at the heart of everything we do. Read the full Editorial by Editor-in-Chief Michael Way and Executive Editor Seema Grewal.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Submit your abstract by 5 April. Final registration deadline: 3 May 2024.
Workshop: Roles of Lipids in Nuclear Homeostasis and Genome Stability
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 14-17 October 2024. Application deadline: 19 April.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.