Ma Cheng-I Jonathan, Brill Julie A
Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Medical Sciences Building, Toronto, ON, Canada.
Commun Integr Biol. 2021 Feb 9;14(1):15-20. doi: 10.1080/19420889.2021.1874663.
Secretory granules (SGs) are organelles responsible for regulated exocytosis of biologically active molecules in professional secretory cells. Maturation of SGs is a crucial process in which cargoes of SGs are processed and activated, allowing them to exert their function upon secretion. Nonetheless, the intracellular trafficking pathways required for SG maturation are not well defined. We recently performed an RNA interference (RNAi) screen in larval salivary glands to identify trafficking components needed for SG maturation. From the screen, we identified several Rab GTPases (Rabs) that affect SG maturation. Expression of constitutively active (CA) and dominant-negative (DN) forms narrowed down the Rabs important for this process to Rab5, Rab9 and Rab11. However, none of these Rabs localizes to the limiting membrane of SGs. In contrast, examination of endogenously YFP-tagged Rabs (YRabs) in larval salivary glands revealed that YRab1 and YRab6 localize to the limiting membrane of immature SGs (iSGs) and SGs. These findings provide new insights into how Rab GTPases contribute to the process of SG maturation.
分泌颗粒(SGs)是负责专业分泌细胞中生物活性分子调节性胞吐作用的细胞器。SGs的成熟是一个关键过程,在此过程中,SGs的货物被加工和激活,使其在分泌时发挥功能。尽管如此,SGs成熟所需的细胞内运输途径仍未明确界定。我们最近在幼虫唾液腺中进行了RNA干扰(RNAi)筛选,以鉴定SGs成熟所需的运输成分。通过筛选,我们鉴定出了几种影响SGs成熟的Rab GTP酶(Rabs)。组成型激活(CA)和显性阴性(DN)形式的表达将此过程中重要的Rabs缩小到Rab5、Rab9和Rab11。然而,这些Rabs均未定位于SGs的界膜。相比之下,对幼虫唾液腺中内源性黄色荧光蛋白标记的Rabs(YRabs)的检测显示,YRab1和YRab6定位于未成熟SGs(iSGs)和SGs的界膜。这些发现为Rab GTP酶如何促进SGs成熟过程提供了新的见解。