Netrins and Neogenin Promote Myotube Formation

Differentiation of skeletal myoblasts into multinucleated myotubes is a multistep process orchestrated by several families of transcription factors, including myogenic bHLH and NFAT proteins. The activities of these factors and formation of myotubes are regulated by signal transduction pathways, but...

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Bibliographic Details
Published in:The Journal of cell biology 2004-11, Vol.167 (3), p.493-504
Main Authors: Kang, Jong-Sun, Yi, Min-Jeong, Zhang, Wei, Feinleib, Jessica L., Cole, Francesca, Krauss, Robert S.
Format: Article
Language:English
Subjects:
Antibodies
Autocrine Communication
Basic Helix-Loop-Helix Transcription Factors
Cadherins
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules - physiology
Cell Differentiation
Cell growth
Cell Line
Cell lines
Cell nucleus
Cellular biology
Cultured cells
DNA-Binding Proteins
Macromolecular Substances
Membrane Glycoproteins - metabolism
Membrane Glycoproteins - physiology
Membrane Proteins - physiology
Muscle development
Muscle fibers
Muscle Fibers, Skeletal - cytology
Myoblasts
Myoblasts - metabolism
Nerve Growth Factors
Nerve Tissue Proteins - physiology
Netrins
NFATC Transcription Factors
Nuclear Proteins
Proteins
Receptors
Transcription Factors
Transcription, Genetic
Tumor Suppressor Proteins - metabolism
Tumor Suppressor Proteins - physiology
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Summary:Differentiation of skeletal myoblasts into multinucleated myotubes is a multistep process orchestrated by several families of transcription factors, including myogenic bHLH and NFAT proteins. The activities of these factors and formation of myotubes are regulated by signal transduction pathways, but few extracellular factors that might initiate such signals have been identified. One exception is a cell surface complex containing promyogenic Ig superfamily members (CDO and BOC) and cadherins. Netrins and their receptors are established regulators of axon guidance, but little is known of their function outside the nervous system. We report here that myoblasts express the secreted factor netrin-3 and its receptor, neogenin. These proteins stimulate myotube formation and enhance myogenic bHLH- and NFAT-dependent transcription. Furthermore, neogenin binds to CDO in a cis fashion, and myoblasts lacking CDO are defective in responding to recombinant netrin. It is proposed that netrin-3 and neogenin may promote myogenic differentiation by an autocrine mechanism as components of a higher order complex of several promyogenic cell surface proteins.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200405039