4.6 Article

δ-catenin-induced dendritic morphogenesis -: An essential role of p190RhoGEF interaction through Akt1-mediated phosphorylation

期刊

JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 2, 页码 977-987

出版社

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M707158200

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资金

  1. NCI NIH HHS [R01 CA111891-01A1, R01 CA111891-03, R01 CA111891, CA11891, R01 CA111891-02] Funding Source: Medline
  2. NIA NIH HHS [R03 AG026630-01, R03 AG026630-02, AG026630, R03 AG026630] Funding Source: Medline

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delta-Catenin was first identified through its interaction with Presenilin-1 and has been implicated in the regulation of dendrogenesis and cognitive function. However, the molecular mechanisms by which delta-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated delta-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of delta-catenin in this interaction. We have also found that delta-catenin overexpression decreased the binding between p190RhoGEF and RhoA, and significantly lowered the levels of GTP-RhoA but not those of GTP-Rac1 and -Cdc42. delta-Catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. delta-Catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, delta-catenin T454A significantly reduced the length and number of mature mushroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of delta-catenin-induced dendrogenesis and spine morphogenesis.

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