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Local Arrangement of Fibronectin by Myofibroblasts Governs Peripheral Nuclear Positioning in Muscle Cells

37 Pages Posted: 13 Apr 2018 Publication Status: Review Complete

See all articles by William Roman

William Roman

University of Lisbon - Instituto de Medicina Molecular (iMM)

João P. Martins

University of Lisbon - Instituto de Medicina Molecular (iMM)

Edgar R. Gomes

University of Lisbon, Faculty of Medicine, Institute of Molecular Medicine

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Abstract

Skeletal muscle cells (myofibers) are rod shaped multinucleated cells surrounded by an ECM basal lamina. In contrast to other cell types, nuclei in myofibers are positioned just below the plasma membrane at the cell periphery. Peripheral nuclear positioning occurs during myogenesis and is driven by myofibril crosslinking and contraction. Here we show that peripheral nuclear positioning is triggered by local accumulation of fibronectin secreted by myofibroblasts. We demonstrate that fibronectin via α5-integrin mediates peripheral nuclear positioning dependent on FAK and Src activation. Finally, we show that Cdc42, downstream of restricted fibronectin activation, is required for myofibril crosslinking but not myofibril contraction. Thus we identify that local activation of integrin by fibronectin secreted by myofibroblasts activates peripheral nuclear positioning in skeletal myofibers.

Suggested Citation

Roman, William and Martins, João P. and Gomes, Edgar R., Local Arrangement of Fibronectin by Myofibroblasts Governs Peripheral Nuclear Positioning in Muscle Cells (2018). Available at SSRN: https://ssrn.com/abstract=3155799 or http://dx.doi.org/10.2139/ssrn.3155799
This version of the paper has not been formally peer reviewed.

William Roman

University of Lisbon - Instituto de Medicina Molecular (iMM)

Av. Professor Egas Moniz
Lisboa, 1649-028
Portugal

João P. Martins

University of Lisbon - Instituto de Medicina Molecular (iMM)

Av. Professor Egas Moniz
Lisboa, 1649-028
Portugal

Edgar R. Gomes (Contact Author)

University of Lisbon, Faculty of Medicine, Institute of Molecular Medicine ( email )

R. Branca Edmée Marques
Lisbon, 1600-276
Portugal

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