Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA.
J Comp Neurol. 2010 Sep 15;518(18):3803-18. doi: 10.1002/cne.22425.
Clathrin-coated vesicles are known to play diverse and pivotal roles in cells. The proper formation of clathrin-coated vesicles is dependent on, and highly regulated by, a large number of clathrin assembly proteins. These assembly proteins likely determine the functional specificity of clathrin-coated vesicles, and together they control a multitude of intracellular trafficking pathways, including those involved in embryonic development. In this study, we focus on two closely related clathrin assembly proteins, AP180 and CALM (clathrin assembly lymphoid myeloid leukemia protein), in the developing embryonic rat brain. We find that AP180 begins to be expressed at embryonic day 14 (E14), but only in postmitotic cells that have acquired a neuronal fate. CALM, on the other hand, is expressed as early as E12, by both neural stem cells and postmitotic neurons. In vitro loss-of-function studies using RNA interference (RNAi) indicate that AP180 and CALM are dispensable for some aspects of embryonic neurogenesis but are required for the growth of postmitotic neurons. These results identify the developmental stage of AP180 and CALM expression and suggest that each protein has distinct functions in neural development.
网格蛋白包被小泡在细胞中发挥着多样且关键的作用。网格蛋白包被小泡的正确形成依赖于大量的网格蛋白组装蛋白,并受其高度调控。这些组装蛋白可能决定了网格蛋白包被小泡的功能特异性,它们共同控制着多种细胞内运输途径,包括参与胚胎发育的途径。在这项研究中,我们关注了发育中胚胎大鼠脑中两种密切相关的网格蛋白组装蛋白,AP180 和 CALM(网格蛋白组装淋巴髓样白血病蛋白)。我们发现,AP180 于胚胎第 14 天(E14)开始表达,但仅在已获得神经元命运的有丝分裂后细胞中表达。另一方面,CALM 在 E12 时就由神经干细胞和有丝分裂后神经元表达。使用 RNA 干扰(RNAi)的体外功能丧失研究表明,AP180 和 CALM 对于胚胎神经发生的某些方面不是必需的,但对于有丝分裂后神经元的生长是必需的。这些结果确定了 AP180 和 CALM 表达的发育阶段,并表明每种蛋白在神经发育中具有不同的功能。