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Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho.

Martinez MC, Ochiishi T, Majewski M, Kosik KS - J. Cell Biol. (2003)

Bottom Line: Under conditions when tyrosine phosphorylation is reduced, delta-catenin binds to cortactin and cells extend unbranched primary processes.When RhoA is inhibited, delta-catenin enhances the effects of Rho inhibition on branching.We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Neurology, Brigham and Women's Hospital and Harvard Medical School, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

ABSTRACT
Delta-catenin is a neuronal protein that contains 10 Armadillo motifs and binds to the juxtamembrane segment of classical cadherins. We report that delta-catenin interacts with cortactin in a tyrosine phosphorylation-dependent manner. This interaction occurs within a region of the delta-catenin sequence that is also essential for the neurite elongation effects. Src family kinases can phosphorylate delta-catenin and bind to delta-catenin through its polyproline tract. Under conditions when tyrosine phosphorylation is reduced, delta-catenin binds to cortactin and cells extend unbranched primary processes. Conversely, increasing tyrosine phosphorylation disrupts the delta-catenin-cortactin complex. When RhoA is inhibited, delta-catenin enhances the effects of Rho inhibition on branching. We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree.

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δ-Catenin–cortactin interaction is regulated by tyrosine phosphorylation. (A) PC12 and δ-PC12 cells were lysed and immunoprecipitated with mAb δ-catenin. Blots were immunolabeled with a mAb δ-catenin or a phosphotyrosine antibody (p-tyr). (B) Hippocampal neurons in culture for 10 d were treated for 5 min with 200 μM H2O2 or 200 μM H2O2 plus 1 mM sodium orthovanadate. Cells were lysed and immunoprecipitated by a mAb δ-catenin. Blots were immunolabeled for mAb δ-catenin, phosphotyrosine, cortactin, and N-cadherin. (C) Hippocampal neurons in culture for 3 wk were treated with BDNF (50 ng/ml) for 1 h, and δ-catenin was immunoprecipitated with a mAb δ-catenin. Blots of the immunoprecipitated products were labeled with mAb δ-catenin, phosphotyrosine, and cortactin antibodies. (D) δ-PC12 cells (pretreated with 100 ng/ml NGF for 36 h) were treated with PP2 (25 μM for 1 h). Immunoprecipitated products were blotted with mAb δ-catenin, phosphotyrosine, and cortactin antibodies.
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fig6: δ-Catenin–cortactin interaction is regulated by tyrosine phosphorylation. (A) PC12 and δ-PC12 cells were lysed and immunoprecipitated with mAb δ-catenin. Blots were immunolabeled with a mAb δ-catenin or a phosphotyrosine antibody (p-tyr). (B) Hippocampal neurons in culture for 10 d were treated for 5 min with 200 μM H2O2 or 200 μM H2O2 plus 1 mM sodium orthovanadate. Cells were lysed and immunoprecipitated by a mAb δ-catenin. Blots were immunolabeled for mAb δ-catenin, phosphotyrosine, cortactin, and N-cadherin. (C) Hippocampal neurons in culture for 3 wk were treated with BDNF (50 ng/ml) for 1 h, and δ-catenin was immunoprecipitated with a mAb δ-catenin. Blots of the immunoprecipitated products were labeled with mAb δ-catenin, phosphotyrosine, and cortactin antibodies. (D) δ-PC12 cells (pretreated with 100 ng/ml NGF for 36 h) were treated with PP2 (25 μM for 1 h). Immunoprecipitated products were blotted with mAb δ-catenin, phosphotyrosine, and cortactin antibodies.

Mentions: The tyrosine phosphorylation state of δ-catenin in δ-PC12 cells and primary neurons differed. δ-Catenin was tyrosine phosphorylated in the δ-PC12 cells (Fig. 6Figure 6.


Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho.

Martinez MC, Ochiishi T, Majewski M, Kosik KS - J. Cell Biol. (2003)

δ-Catenin–cortactin interaction is regulated by tyrosine phosphorylation. (A) PC12 and δ-PC12 cells were lysed and immunoprecipitated with mAb δ-catenin. Blots were immunolabeled with a mAb δ-catenin or a phosphotyrosine antibody (p-tyr). (B) Hippocampal neurons in culture for 10 d were treated for 5 min with 200 μM H2O2 or 200 μM H2O2 plus 1 mM sodium orthovanadate. Cells were lysed and immunoprecipitated by a mAb δ-catenin. Blots were immunolabeled for mAb δ-catenin, phosphotyrosine, cortactin, and N-cadherin. (C) Hippocampal neurons in culture for 3 wk were treated with BDNF (50 ng/ml) for 1 h, and δ-catenin was immunoprecipitated with a mAb δ-catenin. Blots of the immunoprecipitated products were labeled with mAb δ-catenin, phosphotyrosine, and cortactin antibodies. (D) δ-PC12 cells (pretreated with 100 ng/ml NGF for 36 h) were treated with PP2 (25 μM for 1 h). Immunoprecipitated products were blotted with mAb δ-catenin, phosphotyrosine, and cortactin antibodies.
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Related In: Results  -  Collection

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fig6: δ-Catenin–cortactin interaction is regulated by tyrosine phosphorylation. (A) PC12 and δ-PC12 cells were lysed and immunoprecipitated with mAb δ-catenin. Blots were immunolabeled with a mAb δ-catenin or a phosphotyrosine antibody (p-tyr). (B) Hippocampal neurons in culture for 10 d were treated for 5 min with 200 μM H2O2 or 200 μM H2O2 plus 1 mM sodium orthovanadate. Cells were lysed and immunoprecipitated by a mAb δ-catenin. Blots were immunolabeled for mAb δ-catenin, phosphotyrosine, cortactin, and N-cadherin. (C) Hippocampal neurons in culture for 3 wk were treated with BDNF (50 ng/ml) for 1 h, and δ-catenin was immunoprecipitated with a mAb δ-catenin. Blots of the immunoprecipitated products were labeled with mAb δ-catenin, phosphotyrosine, and cortactin antibodies. (D) δ-PC12 cells (pretreated with 100 ng/ml NGF for 36 h) were treated with PP2 (25 μM for 1 h). Immunoprecipitated products were blotted with mAb δ-catenin, phosphotyrosine, and cortactin antibodies.
Mentions: The tyrosine phosphorylation state of δ-catenin in δ-PC12 cells and primary neurons differed. δ-Catenin was tyrosine phosphorylated in the δ-PC12 cells (Fig. 6Figure 6.

Bottom Line: Under conditions when tyrosine phosphorylation is reduced, delta-catenin binds to cortactin and cells extend unbranched primary processes.When RhoA is inhibited, delta-catenin enhances the effects of Rho inhibition on branching.We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Neurology, Brigham and Women's Hospital and Harvard Medical School, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

ABSTRACT
Delta-catenin is a neuronal protein that contains 10 Armadillo motifs and binds to the juxtamembrane segment of classical cadherins. We report that delta-catenin interacts with cortactin in a tyrosine phosphorylation-dependent manner. This interaction occurs within a region of the delta-catenin sequence that is also essential for the neurite elongation effects. Src family kinases can phosphorylate delta-catenin and bind to delta-catenin through its polyproline tract. Under conditions when tyrosine phosphorylation is reduced, delta-catenin binds to cortactin and cells extend unbranched primary processes. Conversely, increasing tyrosine phosphorylation disrupts the delta-catenin-cortactin complex. When RhoA is inhibited, delta-catenin enhances the effects of Rho inhibition on branching. We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree.

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