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The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis

Nature Cell Biology volume 8, pages 227–237 (2006)Cite this article

Abstract

PAR-3 (partitioning-defective gene 3) is essential for cell polarization in many contexts, including axon specification. However, polarity proteins have not been implicated in later steps of neuronal differentiation, such as dendritic spine morphogenesis. Here, we show that PAR-3 is necessary for normal spine development in primary hippocampal neurons. Depletion of PAR-3 causes the formation of multiple filopodia- and lamellipodia-like dendritic protrusions — a phenotype similar to neurons expressing activated Rac. PAR-3 regulates spine formation by binding the Rac guanine nucleotide-exchange factor (GEF) TIAM1, and spatially restricting it to dendritic spines. Thus, a balance of PAR-3 and TIAM1 is essential to modulate Rac–GTP levels and to allow spine morphogenesis.

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Figure 1: Silencing of PAR-3 expression affects spine morphology.
Figure 2: Effects of PAR-3 knockdown are dependent on Rac.
Figure 3: TIAM1 binds PAR-3 and regulates spine formation.
Figure 4: PAR-3 and TIAM1 cooperate in regulating spine formation.
Figure 5: Functional analyses of rescued spines.
Figure 6: PAR-3 regulates spine formation by spatially restricting TIAM1.
Figure 7: Model depicting the mechanism for the effect of PAR-3 on spine morphogenesis.

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Acknowledgements

We thank J. Fawcett and T. Pawson for providing the PAR-3 antibody, X. Chen and L. Gao for constructs and helpful discussions, and Y. Qin for help with culture of the hippocampal neurons. We would also like to extend our gratitude to A. Spang (Friedrich-Miescher-Laboratorium, Tübingen, Germany) and D. Webb (Vanderbilt University, Nashville, TN) for comments on the manuscript. This work was supported by grant GM070902 from the National Institutes of Health.

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  1. Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA, 22908-0577, USA

    Huaye Zhang & Ian G. Macara

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Correspondence to Huaye Zhang.

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Zhang, H., Macara, I. The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nat Cell Biol 8, 227–237 (2006). https://doi.org/10.1038/ncb1368

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