title: BIN1 regulates dynamic t-tubule membrane.
abstract: Cardiac transverse tubules (t-tubules) are specific membrane organelles critical in calcium signaling and excitation-contraction coupling required for beat-to-beat heart contraction. T-tubules are highly branched and form an interconnected network that penetrates the myocyte interior to form junctions with the sarcoplasmic reticulum. T-tubules are selectively enriched with specific ion channels and proteins crucial in calcium transient development necessary in excitation-contraction coupling, thus t-tubules are a key component of cardiac myocyte function. In this review, we focus primarily on two proteins concentrated within the t-tubular network, the L-type calcium channel (LTCC) and associated membrane anchor protein, bridging integrator 1 (BIN1). Here, we provide an overview of current knowledge in t-tubule morphology, composition, microdomains, as well as the dynamics of the t-tubule network. Secondly, we highlight multiple aspects of BIN1-dependent t-tubule function, which includes forward trafficking of LTCCs to t-tubules, LTCC clustering at t-tubule surface, microdomain organization and regulation at t-tubule membrane, and the formation of a slow diffusion barrier within t-tubules. Lastly, we describe progress in characterizing how acquired human heart failure can be attributed to abnormal BIN1 transcription and associated t-tubule remodeling. Understanding BIN1-regulated cardiac t-tubule biology in human heart failure management has the dual benefit of promoting progress in both biomarker development and therapeutic target identification. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
authors.affiliation: Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: TingTing.Hong@cshs.org.
authors.forename: TingTing
authors.initials: T
authors.lastname: Hong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012307:Risk Factors; D012508:Sarcolemma / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D020746:Calcium Channels, L-Type; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins
keywords: BIN1; Cardiomyocyte; Excitation–contraction coupling; Heart failure; Microdomains; T-tubule