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

ABSTRACT: Skeletal muscle cells (myofibers) are rod-shaped multinucleated cells surrounded by an extracellular matrix (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 ?5-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.

SUBMITTER: Roman W

PROVIDER: S-EPMC6035285 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Roman William W Martins João P JP Gomes Edgar R ER

Developmental cell 20180621 1

Skeletal muscle cells (myofibers) are rod-shaped multinucleated cells surrounded by an extracellular matrix (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 demonst ...[more]

PMID: 29937388

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