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.
Shootin1: a protein involved in the organization of an asymmetric signal 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.
Michinori Toriyama, Tadayuki Shimada, Ki Bum Kim, Mari Mitsuba, Eiko Nomura, Kazuhiro Katsuta, Yuichi Sakumura, Peter Roepstorff, Naoyuki Inagaki; Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization . J Cell Biol 9 October 2006; 175 (1): 147–157. doi: https://doi.org/10.1083/jcb.200604160
Download citation file:
Sign in
Client Account
Sign in via your Institution
Sign in via your InstitutionSee also
Email alerts
Advertisement
Advertisement