Abstract
Myofibril assembly results in a regular array of identical sarcomeres in striated muscle. Sarcomere structure is conserved across the animal kingdom, which implies that the mechanisms of myofibril assembly are also likely to be conserved. Recent advances from model genetic systems and insights from stress fibre cell biology have shed light on the mechanisms that set sarcomere spacing and the initial assembly of sarcomere arrays. We propose a model of integrin-dependent cell–matrix adhesion as the starting point for myofibrillogenesis.
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Acknowledgements
We apologize to the authors of the large body of work that we could not cite owing to space constraints. J.C.S. is funded as a member of the EU Framework 6 Network of Excellence 'Myores'. F.S. is a Canadian Institutes of Health Research New Investigator.
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Glossary
- A-band
-
The area of the sarcomere that is spanned by thick filaments.
- Cardiomyocyte
-
A fully differentiated heart muscle cell with a single nucleus.
- Costamere
-
An integrin adhesion site that connects the lateral sarcolemma to the surrounding connective tissue at the level of the Z termini end-to-end in cardiomyocytes.
- Focal adhesion
-
An integrin adhesion site on the basal side of tissue culture cells to which stress fibres attach.
- I-band
-
The area on both sides of the Z-disk that is spanned by thin filaments that do not overlap with thick filaments.
- Integrin adhesion site
-
Any cell–matrix adhesion that is mediated by integrins, for example, a focal adhesion, a costamere or a myotendinous junction.
- Intercalated disc
-
A cadherin adhesion site that connects myofibre termini end-to-end in cardiomyocytes.
- Myoblast
-
A muscle precursor cell with a single nucleus.
- Myotube
-
A multinucleated skeletal muscle cell.
- Myotendinous junction
-
An integrin adhesion site that connects myofibre termini to tendons or tendon cells.
- Premyofibril
-
A myofibril precursor that partly resembles non-muscle cell stress fibres. Premyofibrils contain alternate sarcomeric α-actinin and non-muscle myosin II that originate at integrin-mediated Z-body precursors, called protocostameres, in muscle cells.
- Protocostamere
-
A small integrin adhesion site and Z-body precursor, to which the initial cortical premyofibrils are anchored.
- Sarcolemma
-
The muscle cell membrane.
- Sarcomere
-
The smallest contractile unit of muscle, which is bordered by Z-disks.
- Stress fibre
-
A graded polarity actin filament bundle that has alternate α-actinin and non-muscle myosin II, and is found in non-muscle tissue culture cells.
- Z-body
-
An electron-dense Z-disk precursor that is assembled in association with protocostameres. It contains Z-disk proteins, including ZASP, sarcomeric α-actinin and titin.
- Z-disk
-
The boundary of the sarcomere, at which antiparallel thin filaments are anchored to α-actinin and many other characteristic Z-disk proteins.
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Sparrow, J., Schöck, F. The initial steps of myofibril assembly: integrins pave the way. Nat Rev Mol Cell Biol 10, 293–298 (2009). https://doi.org/10.1038/nrm2634
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