Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors

Naoya Yamashita, Hiroshi Usui, Fumio Nakamura, Sandy Chen, Yukio Sasaki, Tomonobu Hida, Fumikazu Suto, Masahiko Taniguchi, Kohtaro Takei and Yoshio Goshima ()
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Naoya Yamashita: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Hiroshi Usui: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Fumio Nakamura: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Sandy Chen: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Yukio Sasaki: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Tomonobu Hida: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Fumikazu Suto: National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira
Masahiko Taniguchi: Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku
Kohtaro Takei: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku
Yoshio Goshima: Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku

Nature Communications, 2014, vol. 5, issue 1, 1-16

Abstract: Abstract The dendritic targeting of neurotransmitter receptors is vital for dendritic development and function. However, how such localization is established remains unclear. Here we show that semaphorin 3A (Sema3A) signalling at the axonal growth cone is propagated towards the cell body by retrograde axonal transport and drives AMPA receptor GluA2 to the distal dendrites, which regulates dendritic development. Sema3A enhances glutamate receptor interacting protein 1-dependent localization of GluA2 in dendrites, which is blocked by knockdown of cytoplasmic dynein heavy chain. PlexinA (PlexA), a receptor component for Sema3A, interacts with GluA2 at the immunoglobulin-like Plexin-transcription-factor domain (PlexA-IPT) in somatodendritic regions. Overexpression of PlexA-IPT suppresses dendritic localization of GluA2 and induces aproximal bifurcation phenotype in the apical dendrites of CA1 hippocampal neurons. Thus, we propose a control mechanism by which retrograde Sema3A signalling regulates the glutamate receptor localization through trafficking of cis-interacting PlexA with GluA2 along dendrites.

Date: 2014
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DOI: 10.1038/ncomms4424

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