Gujar Mahekta R, Tan Ye Sing, Gao Yang, Wang Hongyan
Neuroscience & Behavioral Disorders Programme, Duke-National University of Singapore Medical School, 169857, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
Proc Natl Acad Sci U S A. 2025 Apr 15;122(15):e2419468122. doi: 10.1073/pnas.2419468122. Epub 2025 Apr 10.
Neural stem cells (NSCs) can self-renew and undergo differentiation via asymmetric division. Dysregulation in the balance between self-renewal and differentiation can lead to tumor formation or neurodevelopmental disorders. However, the regulation of phosphatidylinositol transfer protein (PITP)-dependent PI(4)P pools and myosin localization during asymmetric division in dividing cells is not well established. Here, we show that the Golgi proteins Arf1 and ARFGEF2/Sec71 control asymmetric division of NSCs by facilitating the localization of myosin II regulatory light chain, Sqh, to the NSC cortex. Arf1 can physically associate with Sqh and Vibrator, a type I PITP that stimulates phospholipid PI4K activity for PI(4)P production. Further, Arf1 and Sec71 facilitate PI(4)P localization to the cell cortex of neuroblasts. Our data provide evidence that the Golgi proteins Arf1 and its GEF Sec71 facilitate neuroblast polarity through phospholipid-dependent nonmuscle myosin II cortical localization.
神经干细胞(NSCs)能够自我更新,并通过不对称分裂进行分化。自我更新与分化之间平衡的失调会导致肿瘤形成或神经发育障碍。然而,在分裂细胞的不对称分裂过程中,磷脂酰肌醇转移蛋白(PITP)依赖性PI(4)P池和肌球蛋白定位的调控尚未完全明确。在此,我们表明高尔基体蛋白Arf1和ARFGEF2/Sec71通过促进肌球蛋白II调节轻链Sqh定位于NSC皮质来控制NSCs的不对称分裂。Arf1能够与Sqh以及振动器(一种刺激磷脂PI4K活性以产生PI(4)P的I型PITP)发生物理结合。此外,Arf1和Sec71促进PI(4)P定位于成神经细胞的细胞皮质。我们的数据提供了证据,表明高尔基体蛋白Arf1及其鸟嘌呤核苷酸交换因子Sec71通过磷脂依赖性非肌肉肌球蛋白II皮质定位促进成神经细胞极性。