biostudies-literatureGross PAmerican Heart AssociationBritish Heart FoundationNHLBI NIH HHSHHS | NIH | National Heart, Lung, and Blood InstituteNINDS NIH HHS92-114https://www.ebi.ac.uk/biostudies/studies/S-EPMC7790862biostudies-literatureUnknown128(1)<h4>Rationale</h4>Ca²⁺-induced Ca²⁺ release (CICR) in normal hearts requires close approximation of L-type calcium channels (LTCCs) within the transverse tubules (T-tubules) and RyR (ryanodine receptors) within the junctional sarcoplasmic reticulum. CICR is disrupted in cardiac hypertrophy and heart failure, which is associated with loss of T-tubules and disruption of cardiac dyads. In these conditions, LTCCs are redistributed from the T-tubules to disrupt CICR. The molecular mechanism responsible for LTCCs recruitment to and from the T-tubules is not well known. JPH (junctophilin) 2 enables close association between T-tubules and the junctional sarcoplasmic reticulum to ensure efficient CICR. JPH2 has a so-called joining region that is located near domains that interCirculation researchInteraction of the Joining Region in Junctophilin-2 With the L-Type Ca&lt;sup&gt;2+&lt;/sup&gt; Channel Is Pivotal for Cardiac Dyad Assembly and Intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; Dynamics.PMC7790862P01 HL147841RG/17/13/33173R01 HL147558T32 HL091804R01 HL145177R01 HL13988916PRE30860001R01 HL142271R01 HL136954RF1 NS121379Garbincius JFGross PJohnson JWallner MKubo HGibb AASabri AYu DFeldsott EASanchez-Alonso JLambert JRomero CMLucarelli CVarol EPoulet CRizzo VYang YHouser SRRoss JBerretta RMElrod JChen XEaton DMGorelik JfalseInteraction of the Joining Region in Junctophilin-2 With the L-Type Ca&lt;sup&gt;2+&lt;/sup&gt; Channel Is Pivotal for Cardiac Dyad Assembly and Intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; Dynamics.<h4>Rationale</h4>Ca²⁺-induced Ca²⁺ release (CICR) in normal hearts requires close approximation of L-type calcium channels (LTCCs) within the transverse tubules (T-tubules) and RyR (ryanodine receptors) within the junctional sarcoplasmic reticulum. CICR is disrupted in cardiac hypertrophy and heart failure, which is associated with loss of T-tubules and disruption of cardiac dyads. In these conditions, LTCCs are redistributed from the T-tubules to disrupt CICR. The molecular mechanism responsible for LTCCs recruitment to and from the T-tubules is not well known. JPH (junctophilin) 2 enables close association between T-tubules and the junctional sarcoplasmic reticulum to ensure efficient CICR. JPH2 has a so-called joining region that is located near domains that inter2021-01-01T00:00:00Z2021 Jan2025-04-04T00:38:47.757Z2022-02-11T14:56:25.758ZS-EPMC77908623309246410.1161/circresaha.119.31571510.1161/CIRCRESAHA.119.315715