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Preso regulation of dendritic outgrowth through PI(4,5)P2-dependent PDZ interaction with βPix

Authors

  • Jiwon Mo,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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    • J. Mo. and H. W. Lee. These authors contributed equally to this work

  • Dongmin Lee,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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  • Soontaek Hong,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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  • Seungrie Han,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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  • Hyojin Yeo,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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  • Woong Sun,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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  • Sukwoo Choi,

    1. School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
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  • Hyun Kim,

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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  • Hyun Woo Lee

    1. Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
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    • J. Mo. and H. W. Lee. These authors contributed equally to this work


Hyun Kim and Hyun Woo Lee, 1Department of Anatomy, as above.
E-mail: kimhyun@korea.ac.kr and biocais@korea.ac.kr

Abstract

In neuronal development, dendritic outgrowth and arborization are important for the establishment of neural circuit formation. A previous study reported that PSD-95-interacting regulator of spine morphogenesis (Preso) formed a complex with PAK-interacting exchange factor-beta (βPix) via PSD-95/Dlg/ZO-1 (PDZ) interaction. Here, we report that Preso and its binding protein, βPix, are localized in dendritic growth cones. Knockdown and dominant-negative inhibition of Preso in cultured neurons markedly reduced the dendritic outgrowth but not branching, and led to a decrease in the intensity of βPix and F-actin in neuronal dendritic tips. Moreover, phosphatidylinositol 4,5-bisphosphate (PIP2) induced a conformational change in Preso toward the open PDZ domain and enhanced the interaction with βPix. In addition, the Preso band 4.1 protein, ezrin, radixin and moesin (FERM) domain mutant is unable to interact with PIP2 and it did not rescue the Preso-knockdown effect. These results indicate that PIP2 is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix.

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