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Dab1‐mediated colocalization of multi‐adaptor protein CIN85 with Reelin receptors, A po ER 2 and VLDLR , in neurons
Author(s) -
Fuchigami Takahiro,
Sato Yutaka,
Tomita Yuya,
Takano Tetsuya,
Miyauchi Shinya,
Tsuchiya Yukinori,
Saito Taro,
Kubo Kenichiro,
Nakajima Kazunori,
Fukuda Mitsunori,
Hattori Mitsuharu,
Hisanaga Shinichi
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12045
Subject(s) - reelin , dab1 , signal transducing adaptor protein , colocalization , phosphorylation , microbiology and biotechnology , low density lipoprotein receptor related protein 8 , biology , receptor , biochemistry , lipoprotein , very low density lipoprotein , cholesterol
Reelin‐Dab1 signaling is indispensable for proper positioning of neurons in mammalian brain. Reelin is a glycoprotein secreted from C ajal‐ R eztuis cells in marginal zone of cerebral cortex, and its receptors are A polipoprotein E receptor 2 ( A po ER 2) or very low density lipoprotein receptor ( VLDLR ) expressed on migrating neurons. When Reelin binds to A po ER2 or VLDLR , an adaptor protein Dab1 bound to the receptors undergoes T yr phosphorylation that is essential for Reelin signaling. We reported previously that C dk5‐p35 phosphorylates D ab1 at S er400 and S er491 and the phosphorylation regulates its binding to CIN85 , which is an SH 3‐containing multiadaptor protein involved in endocytic downregulation of receptor‐tyrosine kinases. However, the interaction of CIN85 with Dab1 has not been addressed in neurons. We examined here a possibility that CIN85 has a role in Reelin signaling. We found nonpho‐sphorylated Dab1‐mediated colocalization of CIN85 with A po ER 2. The colocalization of CIN85 with A po ER 2 was increased in neurons stimulated with Reelin repeats 3‐6, an active Reelin fragment. The stimulation recruited CIN85 to domains in plasma membrane where it colocalized with A po ER 2 and Dab1 and then to EEA 1‐labeled early endosomes in the cytoplasm. In addition, Tyr phosphorylation of Dab1 strengthened the binding to CIN85 . These results suggest that CIN85 participates in Reelin signaling through the binding to Dab1.