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lüll The giant protein titin: a major player in myocardial mechanics, signaling, and disease Granzier HL; Labeit SCirc Res 2004[Feb]; 94 (3): 284-95The sarcomere contains, in addition to thin and thick filaments, a filament composed of the giant protein titin (also known as connectin). Titin molecules anchor in the Z-disc and extend to the M-line region of the sarcomere. The majority of titin's I-band region functions as a molecular spring. This spring maintains the precise structural arrangement of thick and thin filaments, and gives rise to passive muscle stiffness; an important determinant of diastolic filling. Earlier work on titin has been reviewed before. In this study, our main focus is on recent findings vis-a-vis titin's molecular spring segments in cardiac titins, including the discovery of fetal cardiac isoforms with novel spring elements. We also discuss new insights regarding the role of titin as a biomechanical sensor and signaling molecule. We will end with focusing on the rapidly growing knowledge regarding titinopathies.|Animals[MESH]|Biomechanical Phenomena[MESH]|Connectin[MESH]|Disease Models, Animal[MESH]|Heart Diseases/*physiopathology[MESH]|Heart/*physiology[MESH]|Humans[MESH]|Mice[MESH]|Muscle Proteins/genetics/*physiology[MESH]|Protein Kinases/genetics/*physiology[MESH]|Signal Transduction/*physiology[MESH] |