Bridging integrator 1 (BIN1) (BIN1)

Bridging integrator 1 (BIN1), specifically the cardiac-specific isoform known as cBIN1 (isoform 13), is a BAR domain-containing protein that is vital for the structural organization of cardiomyocytes [UniProt P46195, Hong et al., 2014]. It is primarily responsible for the formation and maintenance of T-tubules, which are specialized membrane invaginations that allow for synchronized calcium release and muscle contraction [Hong et al., 2014]. In patients with heart failure, cBIN1 levels are often depleted, resulting in the fragmentation of T-tubules and a subsequent decline in cardiac contractile function [Hong et al., 2014, Liu et al., 2020]. Consequently, cBIN1 is being investigated as a therapeutic target, with experimental approaches such as AAV-mediated gene therapy aiming to restore its expression and improve heart function [Liu et al., 2020]. Furthermore, the release of cBIN1 into the blood has been identified as a clinical biomarker, where a low "cBIN1 score" correlates with increased risk and severity of heart failure [Nikolova et al., 2018]. While therapeutic development is promising, care must be taken to ensure cardiac specificity, as BIN1 is also widely expressed in the brain and skeletal muscle [UniProt P46195]. In these tissues, BIN1 dysfunction is linked to Alzheimer's disease and centronuclear myopathy, respectively [UniProt P46195]. Current research focuses on using cardiac-specific promoters in gene therapy to mitigate these risks [Liu et al., 2020]. Overall, cBIN1 represents a novel structural target for treating heart failure by addressing the underlying membrane remodeling [Hong et al., 2014, Liu et al., 2020].

Other names

Amphiphysin 2Amphiphysin-like proteinSH3P9Myc box-dependent-interacting protein 1cBIN1

Restoration of T-tubule microdomains and stabilization of L-type calcium channel (Cav1.2) trafficking to improve excitation-contraction coupling [Hong et al., 2014, Liu et al., 2020].