The planar cell polarity protein Vangl2 bidirectionally regulates dendritic branching in cultured hippocampal neurons.
BACKGROUND
Van Gogh-like (Vangl) 2 is a planar cell polarity (PCP) protein that regulates the induction of polarized cellular and tissue morphology during animal development. In the nervous system, the core PCP signaling proteins have been identified to regulate neuronal maturation. In axonal growth cones, the antagonistic interaction of PCP components makes the tips of filopodia sensitive to guidance cues. However, the molecular mechanism by which the PCP signaling regulates spine and dendritic development remains obscure.


RESULTS
Here we explored the finding that a loss of function of Vangl2 results in a significant reduction in spine density and complexity of dendritic branching. In spite of a previous report, in which the Vangl2 C-terminal TSV motif was shown to be required for the interaction with PSD-95 and the C-terminal intracellular domain was shown to associate with N-cadherin, overexpression of deletion mutants (Vangl2-∆TSV and Vangl2-∆C) had little effect on spine density. However, when an N-terminal region deletion mutant was overexpressed, spine density was slightly down-regulated. Intriguingly, the deletion mutants had a more potent effect on dendritic branching, such that the deletion of the N-terminal region reduced dendritic branching, whereas deletion of the C-terminal region increased it.


CONCLUSIONS
Based on these results, Vangl2, a core PCP signaling pathway component, appears to have a functional role in neural complex formation. Especially in the case of dendritic branching, Vangl2 serves as a molecular hub to regulate neural morphology in opposite directions.
Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan. akarih@yamanashi.ac.jp.
Akari
A
Hagiwara
Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan. misatoy@yamanashi.ac.jp.
Misato
M
Yasumura
Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan. yhida@yamanashi.ac.jp.
Yamato
Y
Hida
KAN Research Institute, Hyogo, Japan. e-inoue@kan.eisai.co.jp.
Eiji
E
Inoue
Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan. tohtsuka@yamanashi.ac.jp.
Toshihisa
T
Ohtsuka
D000818:Animals; D016764:Cell Polarity; D048430:Cell Shape; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017208:Rats, Wistar
D009419:Nerve Tissue Proteins; C000602563:Vangl2 protein, rat