ホスホイノシトール3-キナーゼ（PI3K）は、細胞の遊走、増殖、分化などに関わる重要な脂質代謝酵素である。本研究は、クラスIA PI3K の制御サブユニットであるp85に、従来知られていなかったAP-2結合モチーフが存在し、このモチーフがPI3Kの触媒活性非依存的にクラスリンとダイナミンによるエンドサイトーシスを誘発することを明らかにした。AP-2結合モチーフに変異を持つp85は、接着斑への異常な蓄積を示し、線維芽細胞の細胞遊走速度を上昇させることから、p85のAP-2結合モチーフによるエンドサイトーシスは、PI3Kを接着斑から解離させ、細胞遊走を抑制する働きがあることが示唆された。従来、p85は、PI3K の触媒サブユニットであるp110と結合し、細胞遊走を正に制御する因子であると考えられてきたが、本研究によって、p85には正負２つの面があることが明らかになった。PI3Kが関わるガンや免疫疾患の機序を解明する一助になるものと期待される。 参考文献 [1] Hideaki T. Matsubayashi, Jack Mountain, Tony Yao, Amy F. Peterson, Abhijit Deb Roy, Takanari Inoue, Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP-2-mediated endocytosis, BioRxiv, Posted January 02, 2023. https://doi.org/10.1101/2022.12.31.522383 People tend to have their natural tempo/speed in daily life activities (such as walking, speaking, thinking, etc.) and spontaneous tempo variations in response to dynamically changing environments. Such a delicate, flexible, and spontaneous process could be governed by intrinsic brain rhythms and the harmonic communication between several brainwave frequencies, as suggested by our previous studies (Sun et al., 2019-2022). Moreover, aberrant neural oscillations and coordination may give rise to disorders in motor tempo control (i.e., tremor, slowness, rigidity, imbalance), as widely shown in Parkinson’s disease. Based on our neurophysiological findings and their prognostic value, in which we have established a crucial role of intrinsic personal alpha (8-12Hz) and alpha-dependent oscillatory synchrony in representing spontaneous motor tempo and contexts-dependent motor tempo variations [1], we further propose to examine the effects of individual alpha peak frequency (IAF)-selective neuromodulation over the frontal-striatal circuit on maintaining and improving spontaneous motor performance (i.e., motor speed, stability, and flexibility) among normal aging people using non-invasive brain stimulation [2] and multisensory (visual, auditory, and tactile) frequency-tagging techniques. Our study may lead to novel neurofeedback technology development to help people maintain a naturally motivated state and slow down the motor and cognitive aging processes [3-4]. References [1] Sun, S.* et al. Alpha-dependent oscillatory coupling accounts for the inter-individual difference in spontaneous motor tempo and context-dependent adaptative changes. Oral Presentation. The 45th annual meeting of the Japanese Neuroscience Society, 2022. [2] Zhang, J., Sun, S.* et al. (2023). Breakdown of intention-based outcome evaluation after transient right temporoparietal junction deactivation. Scientific Reports, 13(1), 1259. [3] Sun, S.*. (2023). Cognitive and neural bases of salience-driven incidental learning. bioRxiv. [4] Sun, S.*, et al. (2023). Functional connectivity between the amygdala and prefrontal cortex underlies processing of emotion ambiguity. bioRxiv. ―126―PI3-kinaseによるキナーゼ活性非依存的な細胞遊走の制御機構 Natural human tempo and neurofeedback application Sai Sun (Creative Interdisciplinary Research Division/Information and Systems) 松林英明（新領域創成研究部／生命環境）
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