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Published 9 October 2006. doi:10.1083/jcb.200604160
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 1, 147-157
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Article

 Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization

Michinori Toriyama1, Tadayuki Shimada1, Ki Bum Kim1, Mari Mitsuba1, Eiko Nomura1, Kazuhiro Katsuta1, Yuichi Sakumura2, Peter Roepstorff3, and Naoyuki Inagaki1

1 Division of Signal Transduction and 2 Bioinformatics Unit, Nara Institute of Science and Technology, Ikoma 630-0192, Japan
3 Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark

Correspondence to Naoyuki Inagaki: ninagaki{at}bs.naist.jp

Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We describe a novel protein, named shootin1, that became up-regulated during polarization of hippocampal neurons and began fluctuating accumulation among multiple neurites. Eventually, shootin1 accumulated asymmetrically in a single neurite, which led to axon induction for polarization. Disturbing the asymmetric organization of shootin1 by excess shootin1 disrupted polarization, whereas repressing shootin1 expression inhibited polarization. Overexpression and RNA interference data suggest that shootin1 is required for spatially localized phosphoinositide-3-kinase activity. Shootin1 was transported anterogradely to the growth cones and diffused back to the soma; inhibiting this transport prevented its asymmetric accumulation in neurons. We propose that shootin1 is involved in the generation of internal asymmetric signals required for neuronal polarization.

M. Toriyama and T. Shimada contributed equally to this paper.

K.B. Kim's present address is Laboratory of Cell Signal Transduction, School of Life Science and Biotechnology, Korea University, Seoul, 136-701 Korea.

Abbreviations used in this paper: 2DE, 2D electrophoresis; CMFDA, 5-chloromethylfluorescein diacetate; DIV, day in vitro; E, embryonic day; miRNA, microRNA; mRFP, monomeric red fluorescent protein; P, postnatal day; PI 3-kinase, phosphoinositide-3-kinase.


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