On the footsteps of Triadin and its role in skeletal muscle

Abstract

Calcium is a crucial element for striated muscle function. As such, myoplasmic free Ca²⁺ concentration is delicately regulated through the concerted action of multiple Ca²⁺ pathways that relay excitation of the plasma membrane to the intracellular contractile machinery. In skeletal muscle, one of these major Ca²⁺ pathways is Ca²⁺ release from intracellular Ca²⁺ stores through type-1 ryanodine receptor/Ca²⁺ release channels (RyR1), which positions RyR1 in a strategic cross point to regulate Ca²⁺ homeostasis. This major Ca²⁺ traffic point appears to be highly sensitive to the intracellular environment, which senses through a plethora of chemical and protein-protein interactions. Among these modulators, perhaps one of the most elusive is Triadin, a muscle-specific protein that is involved in many crucial aspect of muscle function. This family of proteins mediates complex interactions with various Ca²⁺ modulators and seems poised to be a relevant modulator of Ca²⁺ signaling in cardiac and skeletal muscles. The purpose of this review is to examine the most recent evidence and current understanding of the role of Triadin in muscle function, in general, with particular emphasis on its contribution to Ca²⁺ homeostasis.

Keywords: Excitation-contraction coupling, Triadin-null, Calcium release, Ryanodine receptor, FKBP12, Resting calcium