BIN1 regulates dynamic t-tubule membrane

Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1839-47. doi: 10.1016/j.bbamcr.2015.11.004. Epub 2015 Nov 11.


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.

Keywords: BIN1; Cardiomyocyte; Excitation–contraction coupling; Heart failure; Microdomains; T-tubule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling
  • Genetic Predisposition to Disease
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Humans
  • Membrane Microdomains / genetics
  • Membrane Microdomains / metabolism*
  • Membrane Potentials
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Transport
  • Risk Factors
  • Sarcolemma / metabolism*
  • Sarcolemma / pathology
  • Transcription, Genetic
  • Tumor Suppressor Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • BIN1 protein, human
  • Calcium Channels, L-Type
  • Nuclear Proteins
  • Tumor Suppressor Proteins