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Netrins and neogenin promote myotube formation.

Kang JS, Yi MJ, Zhang W, Feinleib JL, Cole F, Krauss RS - J. Cell Biol. (2004)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.

ABSTRACT
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.

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Netrin-2 requires neogenin to stimulate myotube formation. (A) Western blot analysis of neogenin production by stable control (−) and neogenin RNAi (+) vector transfectants. (B) Photomicrographs of the cells from A were treated with 5% FBS plus or minus netrin-2 for 24 h, and fixed and stained with an antibody to MHC. Bar, 0.2 mm. (C) Quantification of myotube formation. Values represent means of triplicate determinations ± 1 SD.
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fig5: Netrin-2 requires neogenin to stimulate myotube formation. (A) Western blot analysis of neogenin production by stable control (−) and neogenin RNAi (+) vector transfectants. (B) Photomicrographs of the cells from A were treated with 5% FBS plus or minus netrin-2 for 24 h, and fixed and stained with an antibody to MHC. Bar, 0.2 mm. (C) Quantification of myotube formation. Values represent means of triplicate determinations ± 1 SD.

Mentions: To assess whether netrin-2 exerted its effects on myotube formation in a manner dependent on neogenin, a C2C12 cell derivative that stably expressed the neogenin RNAi vector was generated; these cells expressed considerably less neogenin than control transfectants and produced fewer and smaller myotubes than control transfectants when shifted to DME/5% FBS for 24 h (Fig. 5, A–C). When the control cells were treated with netrin-2 under these conditions they behaved similarly to parental C2C12 cells, forming larger myotubes with more nuclei. In contrast, the neogenin RNAi-expressing cells were not affected by netrin-2 (Fig. 5, B and C). Therefore, it is concluded that the ability of netrin-2 to promote myotube formation by C2C12 cells depends on the netrin receptor, neogenin.


Netrins and neogenin promote myotube formation.

Kang JS, Yi MJ, Zhang W, Feinleib JL, Cole F, Krauss RS - J. Cell Biol. (2004)

Netrin-2 requires neogenin to stimulate myotube formation. (A) Western blot analysis of neogenin production by stable control (−) and neogenin RNAi (+) vector transfectants. (B) Photomicrographs of the cells from A were treated with 5% FBS plus or minus netrin-2 for 24 h, and fixed and stained with an antibody to MHC. Bar, 0.2 mm. (C) Quantification of myotube formation. Values represent means of triplicate determinations ± 1 SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172498&req=5

fig5: Netrin-2 requires neogenin to stimulate myotube formation. (A) Western blot analysis of neogenin production by stable control (−) and neogenin RNAi (+) vector transfectants. (B) Photomicrographs of the cells from A were treated with 5% FBS plus or minus netrin-2 for 24 h, and fixed and stained with an antibody to MHC. Bar, 0.2 mm. (C) Quantification of myotube formation. Values represent means of triplicate determinations ± 1 SD.
Mentions: To assess whether netrin-2 exerted its effects on myotube formation in a manner dependent on neogenin, a C2C12 cell derivative that stably expressed the neogenin RNAi vector was generated; these cells expressed considerably less neogenin than control transfectants and produced fewer and smaller myotubes than control transfectants when shifted to DME/5% FBS for 24 h (Fig. 5, A–C). When the control cells were treated with netrin-2 under these conditions they behaved similarly to parental C2C12 cells, forming larger myotubes with more nuclei. In contrast, the neogenin RNAi-expressing cells were not affected by netrin-2 (Fig. 5, B and C). Therefore, it is concluded that the ability of netrin-2 to promote myotube formation by C2C12 cells depends on the netrin receptor, neogenin.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.

ABSTRACT
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.

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