Shootin1: A protein involved in the organization of an asymmetric signal for neuronal polarization.
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.
Toriyama
Michinori
M
Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0192, Japan.
Shimada
Tadayuki
T
Kim
Ki Bum
KB
Mitsuba
Mari
M
Nomura
Eiko
E
Katsuta
Kazuhiro
K
Sakumura
Yuichi
Y
Roepstorff
Peter
P
Inagaki
Naoyuki
N
D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity; D005786:Gene Expression Regulation; D020439:Growth Cones / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D040901:Proteomics; D051381:Rats; D016415:Sequence Alignment
D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; C514975:Shtn1 protein, rat