Calcium-dependent titin-thin filament interactions in muscle: observations and theory.

摘要: Gaps in our understanding of muscle mechanics demonstrate that the current model is incomplete. Increasingly, it appears a role for titin active contraction might help to fill these gaps. While such increasingly accepted, underlying molecular mechanisms remain unclear. The goals this paper are review recent studies demonstrating Ca2+-dependent interactions between N2A and actin vitro, explore theoretical predictions behavior based on interaction, experimental data related predictions. In study, we demonstrated Ca2+ increases association constant F-actin; rupture forces reduce sliding velocity F-actin reconstituted thin filaments motility assays. Preliminary support Ig83, but other Ig domains region may also be involved. Two mechanical consequences inescapable if binds sarcomeres: (1) length titin's freely extensible I-band should decrease upon activation; (2) binding increase stiffness muscle. Experimental observations properties characterize wild type muscles, not muscles from mdm mice with small deletion titin, including part Ig83. Given new vitro evidence actin, time skepticism give way further investigation.