Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an emerging biomarker of heart muscle health

Abstract

In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17)plays a crucial role in organizing membrane microfolds within cardiac t-tubules. These cBIN1-induced microfolds form functional dyad microdomains by trafficking L-type calcium channels (LTCC) to t-tubule membrane and recruiting ryanodine receptors (RyR) to junctional sarcoplasmic reticulum membrane. When cBIN1 is transcriptionally reduced as occurs in heart failure, cBIN1-microfolds are disrupted and fail to form LTCC and RyR couplons. As a result, impaired dyad formation limits excitation-contraction coupling thus cardiac contractility, and accumulation of orphaned leaky RyRs outside of dyads increases ventricular arrhythmias. Reduced myocardial BIN1 in heart failure is also detectable at the blood level, and plasma BIN1 level predicts heart failure progression and future arrhythmias in cardiomyopathy patients. Here we will review the recent progress in BIN1-related cardiomyocyte biology studies and discuss the diagnostic and predictive values of cBIN1 in future clinical use. heart failure, cBIN1, t-tubules, calcium transient, arrhythmias Citation:Zhou, K., and Hong, T. (2017). Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an emerging biomarker of heart muscle health.

Abnormal expression of miR-331 leads to impaired heart function

“…On the other hand, the factors underlying E-C coupling efficiency include sarcoplasmic reticulum (SR). RyRs sensitivity [16], SERCA function [17,18] as well as T-tubule structure [19]. In the present study, miR-331-3p was not predicted to bind either RyR2 or SERCA mRNA.…”

Genomic footprints of dryland stress adaptation in Egyptian fat-tail sheep and their divergence from East African and western Asia cohorts

“…They have been observed in skeletal muscles of endurance athletes and their activation entrains complex pathways that enhance physical 73 and racing performance 74 . Isoforms of BIN1 , are important in the formation of transverse tubules which play a role in skeletal and cardiac muscle contractility and relation 75 , 76 . The selection of MSTN , BIN1 and HIF-1 associated genes could have arisen as an adaptive response to endure physical exhaustion arising from long-term long distance walking.…”

Exogenous Cardiac Bridging Integrator 1 Benefits Mouse Hearts With Pre-existing Pressure Overload-Induced Heart Failure

“…More recently, we found that cBIN1-microdomain is also critical in organizing the intracellular distribution of SERCA2a for diastolic calcium regulation ( Liu et al, 2020 ). In HF, cBIN1-microdomains are disrupted due to transcriptional reduction in cBIN1 ( Hong et al, 2012b ; Caldwell et al, 2014 ; Zhou and Hong, 2017 ), impairing dyad formation, calcium transient regulation, and cardiac contractility. Reduced myocardial cBIN1 can be detected in human blood, a result of cBIN1-membrane turnover and microparticle release ( Xu et al, 2017 ).…”