取决于HOPS的溶酶体融合控制了Rab19在两极化上皮细胞中产生纤维细胞的可用性
Huxley K Hoffman1, Rytis Prekeris1
1Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Journal of cell science
|September 4, 2023
概括
扰乱 lysosomal 融合通过错位化 Rab19 蛋白质来损害纤维生成,Rab19 蛋白质对于清除actin至关重要,并使极化表皮细胞中的初级纤维生长.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 机体生物学 机体生物学
背景情况:
- 初级毛是发展和恒常状态的重要感官器官.
- 在两极化上皮细胞中的生需要Rab19来清除角性动蛋白,以促进毛细胞的生长.
- 众所周知,同型融合和蛋白质分类 (HOPS) 复合体参与纤维细胞生成,但其与溶酶体融合的联系尚不清楚.
研究的目的:
- 调查HOPS复合体在溶酶体融合中的功能与其在纤维生成中的作用之间的关系.
- 阐明HOPS中断影响Rab19和在纤毛发育过程中的actin清除的机制.
- 为了确定Rab19是否具有超越纤毛发育的作用.
主要方法:
- 研究了干扰HOPS-依赖的溶酶体融合对actin清除和纤毛发育的影响.
- 检查了Rab19在细胞中受 lysosomal 融合干扰的局部化和功能.
- 评估了Rab19在内解体体货物贩运中的作用.
主要成果:
- 干扰HOPS-依赖的溶酶体融合间接损害了actin清除和纤维细胞生成.
- 这种损伤是由于Rab19对基底体的向受损,特别是在两极化上皮细胞中.
- 发现Rab19在内溶性体货物贩运中发挥作用,除了其在纤毛发育中的作用外.
结论:
- 通过HOPS介导的溶酶体融合,通过确保Rab19在基底体上可用,间接地要求纤维生成.
- lysosomal 融合的抑制导致 Rab19 在晚期内体上积聚,从基底体中耗尽它.
- 这种Rab19的枯竭扰乱了两极化上皮细胞中的actin清除和纤毛发育,突出显示了 lysosomal贩运和初级纤毛形成之间的新联系.
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