title: Is titin a 'winding filament'? A new twist on muscle contraction.
abstract: Recent studies have demonstrated a role for the elastic protein titin in active muscle, but the mechanisms by which titin plays this role remain to be elucidated. In active muscle, Ca(2+)-binding has been shown to increase titin stiffness, but the observed increase is too small to explain the increased stiffness of parallel elastic elements upon muscle activation. We propose a 'winding filament' mechanism for titin's role in active muscle. First, we hypothesize that Ca(2+)-dependent binding of titin's N2A region to thin filaments increases titin stiffness by preventing low-force straightening of proximal immunoglobulin domains that occurs during passive stretch. This mechanism explains the difference in length dependence of force between skeletal myofibrils and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as motors that pull thin filaments towards the M-line, but also as rotors that wind titin on the thin filaments, storing elastic potential energy in PEVK during force development and active stretch. Energy stored during force development can be recovered during active shortening. The winding filament hypothesis accounts for force enhancement during stretch and force depression during shortening, and provides testable predictions that will encourage new directions for research on mechanisms of muscle contraction.
authors: Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640, USA. kiisa.nishikawa@nau.edu
authors: Kiisa C
authors: KC
authors: Nishikawa
authors: Jenna A
authors: JA
authors: Monroy
authors: Theodore E
authors: TE
authors: Uyeno
authors: Sang Hoon
authors: SH
authors: Yeo
authors: Dinesh K
authors: DK
authors: Pai
authors: Stan L
authors: SL
authors: Lindstedt
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D064211:Connectin; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009129:Muscle Tonus; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D012518:Sarcomeres / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000199:Actins; D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases; D002118:Calcium