Vinculin and talin: focus on the myocardium

Abstract

Cardiomyopathy is a heart muscle disease caused by decreased contractility of the ventricles leading to heart failure and premature death. Multiple conditions like ischemic heart disease (atherosclerosis), hypertension, diabetes, viral infection, alcohol abuse, obesity and genetic mutations can lead to cardiomyopathy. Single gene mutations in sarcomeric proteins, Z-disk-associated proteins, membrane/associated proteins, intermediate filaments, calcium cycle proteins as well as in modifier genes have been linked to cardiomyopathy. Clinical practice guidelines have been formulated by the American Heart Association and the Heart Failure Association of America on how to genetically evaluate patients with cardiomyopathy. To illustrate the concept that alterations in genes cause cardiovascular disease, this review will focus on two membrane-associated proteins, vinculin and talin. We will discuss the general function of vinculin/metavinulin as well as talin1 and talin2, with emphasis on what is understood about their role in the cardiac myocyte and in whole heart.

Figure 1. Costameric Proteins and the Intercalated Disk of two adjacent cardiac myocytes

Shown are some of the key structural elements of the costameric protein complex of the cardiac myocyte, including ones linked to the integrin-talin-vinculin axis, as well as the dystrophic-glycoprotein complex (DGC). The intercalated disk (ICD) structure providing mechanical and electrical linkage of myocytes is also shown. The ICD mechanical linkages include the desmosomes and the adherens (cadherin-containing) junctions, while electrical coupling of cells occurs at gap junctions (gap j.) which contain connexins (Cx) such as Cx43. This diagram is provided to orient the reader to the location of vinculin and talin (arrows) within the cell, but is clearly a simplified version of costamere and ICD.