LIS1-dependent retrograde translocation of excitatory synapses in developing interneuron dendrites

Izumi Kawabata, Yutaro Kashiwagi, Kazuki Obashi, Masamichi Ohkura, Junichi Nakai, Anthony Wynshaw-Boris, Yuchio Yanagawa and Shigeo Okabe ()
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Izumi Kawabata: Graduate School of Medicine, University of Tokyo
Yutaro Kashiwagi: Graduate School of Medicine, University of Tokyo
Kazuki Obashi: Graduate School of Medicine, University of Tokyo
Masamichi Ohkura: Saitama University Brain Science Institute
Junichi Nakai: Saitama University Brain Science Institute
Anthony Wynshaw-Boris: Institute for Human Genetics, UCSF School of Medicine
Yuchio Yanagawa: Gunma University Graduate School of Medicine
Shigeo Okabe: Graduate School of Medicine, University of Tokyo

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: Abstract Synaptic remodelling coordinated with dendritic growth is essential for proper development of neural connections. After establishment of synaptic contacts, synaptic junctions are thought to become stationary and provide fixed anchoring points for further dendritic growth. However, the possibility of active translocation of synapses along dendritic protrusions, to guide the proper arrangement of synaptic distribution, has not yet been fully investigated. Here we show that immature dendrites of γ-aminobutyric acid-positive interneurons form long protrusions and that these protrusions serve as conduits for retrograde translocation of synaptic contacts to the parental dendrites. This translocation process is dependent on microtubules and the activity of LIS1, an essential regulator of dynein-mediated motility. Suppression of this retrograde translocation results in disorganized synaptic patterns on interneuron dendrites. Taken together, these findings suggest the existence of an active microtubule-dependent mechanism for synaptic translocation that helps in the establishment of proper synaptic distribution on dendrites.

Date: 2012
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DOI: 10.1038/ncomms1736

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