Localized LoxL3-Dependent Fibronectin Oxidation Regulates Myofiber Stretch and Integrin-Mediated Adhesion

Ortal Kraft-Sheleg, Shelly Zaffryar-Eilot, Olga Genin, Wesal Yaseen, Sharon Soueid-Baumgarten, Ofra Kessler, Tatyana Smolkin, Gal Akiri, Gera Neufeld, Yuval Cinnamon, Peleg Hasson

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


For muscles to function, myofibers have to stretch and anchor at the myotendinous junction (MTJ), a region rich in extracellular matrix (ECM). Integrin signaling is required for MTJ formation, and mutations affecting the cascade lead to muscular dystrophies in mice and humans. Underlying mechanisms for integrin activation at the MTJ and ECM modifications regulating its signaling are unclear. We show that lysyl oxidase-like 3 (LoxL3) is a key regulator of integrin signaling that ensures localized control of the cascade. In LoxL3 mutants, myofibers anchor prematurely or overshoot to adjacent somites, and are loose and lack tension. We find that LoxL3 complexes with and directly oxidizes Fibronectin (FN), an ECM scaffold protein and integrin ligand enriched at the MTJ. We identify a mechanism whereby localized LoxL3 secretion from myofiber termini oxidizes FN, enabling enhanced integrin activation at the tips of myofibers and ensuring correct positioning and anchoring of myofibers along the MTJ.

Original languageEnglish
Pages (from-to)550-561
Number of pages12
JournalDevelopmental Cell
Issue number5
StatePublished - 7 Mar 2016
Externally publishedYes

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© 2016 Elsevier Inc.


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