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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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Inhibition of Rho in the presence of δ-catenin enhances branch formation. (A) PC12 cells treated with NGF for 36 h were transfected with GFP (a), GFP and RhoV14 (b), GFP and C3 exotoxin (c). A second set of NGF-treated PC12 cells were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 exotoxin (f). Note the small branches in GFP–δ-catenin–C3-transfected cells (f, arrows). Bar, 5 μM. (B, a) PC12 and δ-PC12 cells transfected with GFP alone or cotransfected with GFP and C3 exotoxin. Neurite length and number of primary and secondary processes of C3-treated cells were quantified and expressed relative to those of untreated cells. (b) GFP-transfected PC12 and δ-PC12 cells were treated with the Rho kinase inhibitor Y27632 (10 μM) for 1 h before fixation. Total process length and number of primary and secondary processes were quantified relative to those of untreated cells. (C) Hippocampal neurons plated for 8 d were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 (f). As control, GFP (a), GFP plus RhoV14 (b), and GFP plus C3 (c) were transfected. Cells were fixed 24 h after transfection. Bar, 15 μM. Quantification of the length and number of protrusions with asterisks indicating significant differences relative to transfections with δ-catenin alone indicated by GFP-δ.
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fig9: Inhibition of Rho in the presence of δ-catenin enhances branch formation. (A) PC12 cells treated with NGF for 36 h were transfected with GFP (a), GFP and RhoV14 (b), GFP and C3 exotoxin (c). A second set of NGF-treated PC12 cells were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 exotoxin (f). Note the small branches in GFP–δ-catenin–C3-transfected cells (f, arrows). Bar, 5 μM. (B, a) PC12 and δ-PC12 cells transfected with GFP alone or cotransfected with GFP and C3 exotoxin. Neurite length and number of primary and secondary processes of C3-treated cells were quantified and expressed relative to those of untreated cells. (b) GFP-transfected PC12 and δ-PC12 cells were treated with the Rho kinase inhibitor Y27632 (10 μM) for 1 h before fixation. Total process length and number of primary and secondary processes were quantified relative to those of untreated cells. (C) Hippocampal neurons plated for 8 d were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 (f). As control, GFP (a), GFP plus RhoV14 (b), and GFP plus C3 (c) were transfected. Cells were fixed 24 h after transfection. Bar, 15 μM. Quantification of the length and number of protrusions with asterisks indicating significant differences relative to transfections with δ-catenin alone indicated by GFP-δ.

Mentions: The pattern of δ-catenin process elaboration could be qualitatively changed when PC12 cells, treated with NGF for 36 h, also expressed the C3 exotoxin, a specific Rho GTPase inhibitor derived from C. difficile, which inhibits Rho by ADP ribosylation (Boquet, 1999). δ-Catenin greatly enhanced the elaboration of branches induced by Rho inhibition (Fig. 9, A and B)Figure 9.


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)

Inhibition of Rho in the presence of δ-catenin enhances branch formation. (A) PC12 cells treated with NGF for 36 h were transfected with GFP (a), GFP and RhoV14 (b), GFP and C3 exotoxin (c). A second set of NGF-treated PC12 cells were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 exotoxin (f). Note the small branches in GFP–δ-catenin–C3-transfected cells (f, arrows). Bar, 5 μM. (B, a) PC12 and δ-PC12 cells transfected with GFP alone or cotransfected with GFP and C3 exotoxin. Neurite length and number of primary and secondary processes of C3-treated cells were quantified and expressed relative to those of untreated cells. (b) GFP-transfected PC12 and δ-PC12 cells were treated with the Rho kinase inhibitor Y27632 (10 μM) for 1 h before fixation. Total process length and number of primary and secondary processes were quantified relative to those of untreated cells. (C) Hippocampal neurons plated for 8 d were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 (f). As control, GFP (a), GFP plus RhoV14 (b), and GFP plus C3 (c) were transfected. Cells were fixed 24 h after transfection. Bar, 15 μM. Quantification of the length and number of protrusions with asterisks indicating significant differences relative to transfections with δ-catenin alone indicated by GFP-δ.
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Related In: Results  -  Collection

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fig9: Inhibition of Rho in the presence of δ-catenin enhances branch formation. (A) PC12 cells treated with NGF for 36 h were transfected with GFP (a), GFP and RhoV14 (b), GFP and C3 exotoxin (c). A second set of NGF-treated PC12 cells were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 exotoxin (f). Note the small branches in GFP–δ-catenin–C3-transfected cells (f, arrows). Bar, 5 μM. (B, a) PC12 and δ-PC12 cells transfected with GFP alone or cotransfected with GFP and C3 exotoxin. Neurite length and number of primary and secondary processes of C3-treated cells were quantified and expressed relative to those of untreated cells. (b) GFP-transfected PC12 and δ-PC12 cells were treated with the Rho kinase inhibitor Y27632 (10 μM) for 1 h before fixation. Total process length and number of primary and secondary processes were quantified relative to those of untreated cells. (C) Hippocampal neurons plated for 8 d were transfected with GFP–δ-catenin (d), GFP–δ-catenin plus RhoV14 (e), or GFP–δ-catenin plus C3 (f). As control, GFP (a), GFP plus RhoV14 (b), and GFP plus C3 (c) were transfected. Cells were fixed 24 h after transfection. Bar, 15 μM. Quantification of the length and number of protrusions with asterisks indicating significant differences relative to transfections with δ-catenin alone indicated by GFP-δ.
Mentions: The pattern of δ-catenin process elaboration could be qualitatively changed when PC12 cells, treated with NGF for 36 h, also expressed the C3 exotoxin, a specific Rho GTPase inhibitor derived from C. difficile, which inhibits Rho by ADP ribosylation (Boquet, 1999). δ-Catenin greatly enhanced the elaboration of branches induced by Rho inhibition (Fig. 9, A and B)Figure 9.

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.

Show MeSH
Related in: MedlinePlus