Abstract：
Primary cilia are antenna-like organelles that regulate growth and development via extracellular signals. However, the molecular mechanisms underlying cilia dynamics, particularly those regulating their disassembly, are not well understood. Here, we show that leucine-rich repeat kinase 1 (LRRK1) plays a role in regulating cilia disassembly. The depletion of LRRK1 impairs primary cilia resorption following serum stimulation in cultured cells. Polo-like kinase 1 (PLK1) plays an important role in this process. During ciliary resorption, PLK1 phosphorylates LRRK1 at the primary cilia base, resulting in its activation. We identified nuclear distribution protein nudE-like 1 (NDEL1), which is known to positively regulate cilia disassembly, as a target of LRRK1 phosphorylation. Whereas LRRK1 phosphorylation of NDEL1 on Ser-155 promotes NDEL1 interaction with the intermediate chains of cytoplasmic dynein-2, it is also crucial for triggering ciliary resorption through dynein-2-driven retrograde intraflagellar transport. These findings provide evidence that a novel PLK1-LRRK1-NDEL1 pathway regulates cilia disassembly.
摘要：
初级纤毛是通过细胞外信号调节生长和发育的天线样细胞器。然而,纤毛动力学的分子机制，特别是那些规范它们拆卸的人，不是很了解。这里,我们表明富含亮氨酸的重复激酶1（LRRK1）在调节纤毛分解中起作用。LRRK1的消耗会损害培养细胞中血清刺激后的初级纤毛吸收。Polo样激酶1（PLK1）在此过程中起着重要作用。在纤毛吸收期间，PLK1在初级纤毛碱基处磷酸化LRRK1，导致其激活。我们鉴定了核分布蛋白nudE样1(NDEL1)，众所周知，它能积极调节纤毛的分解，作为LRRK1磷酸化的靶标。尽管Ser-155上NDEL1的LRRK1磷酸化促进NDEL1与细胞质动力蛋白2的中间链相互作用，但它对于通过动力蛋白2驱动的逆行步行内运输触发纤毛吸收也至关重要。这些发现提供了新的PLK1-LRRK1-NDEL1通路调节纤毛分解的证据。
