Analysis of a Novel Protein Shootin1, which is involved in organization of an asymmetric signal for neuronal polarization

点击翻译按钮获取中文摘要

The basic function of neurons is to receive, integrate and transmit signals. To do so, most neurons develop polarity by forming a single axon and multiple dendrites. 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 recently described an intracellular protein, shootin1, which plays a critical role in neuronal polarization. During the symmetry breaking step, shootin1 becomes up-regulated, undergoes a fluctuating accumulation in growth cones at neurite tips, and eventually accumulates asymmetrically in a single growth cone. Accumulation of shootin1 in nerve growth cones also enhanced neurite elongation. In this study, we examined molecular mechanisms for shootin1-induced neurite outgrowth and the mechanisms for generation of asymmetric signal of shootin1. Shootin1 not only acted as a upstream regulator of PI 3-kinase but also enhanced neurite elongation, by linking a cell adhesion molecule Ll-CAM to actin filament retrograde flow as a "clutch molecule". We also obtained data to suggest that positive feedback amplification of shootin1 signal in growth cones contributes to generation of asymmetric shootin 1 signals during neuronal polarization. We also succeeded in generation of shootin 1 knockout mice, and are currently analyzing their phenotypes.