Article abstract
Nature Neuroscience 10, 963 - 969 (2007)
Published online: 8 July 2007 | doi:10.1038/nn1933
Opposing roles in neurite growth control by two seven-pass transmembrane cadherins
Yasuyuki Shima1,2,6, Shin-ya Kawaguchi2,3, Kazuyoshi Kosaka3, Manabu Nakayama4, Mikio Hoshino5, Yoichi Nabeshima5, Tomoo Hirano2,3 & Tadashi Uemura1,2
Abstract
The growth of neurites (axon and dendrite) should be appropriately regulated by their interactions in the development of nervous systems where a myriad of neurons and their neurites are tightly packed. We show here that mammalian seven-pass transmembrane cadherins Celsr2 and Celsr3 are activated by their homophilic interactions and regulate neurite growth in an opposing manner. Both gene-silencing and coculture assay with rat neuron cultures showed that Celsr2 enhanced neurite growth, whereas Celsr3 suppressed it, and that their opposite functions were most likely the result of a difference of a single amino acid residue in the transmembrane domain. Together with calcium imaging and pharmacological analyses, our results suggest that Celsr2 and Celsr3 fulfill their functions through second messengers, and that differences in the activities of the homologs results in opposite effects in neurite growth regulation.
- Graduate School of Biostudies, Yoshida Konoecho, Kyoto University, Sakyo-Ku, Kyoto, Kyoto 606–8501, Japan.
- CREST, Japan Science and Technology Agency, 3–5 Chiyoda, Tokyo 102–0075, Japan.
- Graduate School of Science, Kitashirakawa Oiwakecho, Kyoto University, Sakyo-ku, Kyoto, Kyoto 606–8501, Japan.
- Kazusa DNA Research Institute, 2–6–7 Kazusa Kamatari, Kizarasu, Chiba 292–0818, Japan.
- Graduate School of Medicine, Yoshida Konoecho,Kyoto University, Sakyo-ku, Kyoto, Kyoto 606–8501, Japan.
- Present address: Department of Biology, Brandeis University MS 008, 415 South Street, Waltham, Massachusetts 02454–9110, USA.
Correspondence to: Tadashi Uemura1,2 e-mail: tauemura@lif.kyoto-u.ac.jp
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