Distinct Roles of Myosin Va in Membrane Remodeling and Exocytosis of Secretory Granules
Distinct Roles of Myosin Va in Membrane Remodeling and Exocytosis of Secretory Granules
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DOI：
10.1111/j.1600-0854.2010.01048.x
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发表时间：
2010-05-01
期刊：
影响因子：
4.5
通讯作者：
Gerdes, Hans-Hermann
中科院分区：
文献类型：
--
作者：
Koegel, Tanja;Rudolf, Ruediger;Gerdes, Hans-Hermann
神经内分泌PC 12细胞的含激素和神经肽的分泌颗粒（SG）作为未成熟的SG在反高尔基体网络处形成。这些中间体在复杂的成熟过程中转化为成熟的SG，包括基质浓缩、货物蛋白的加工以及网格蛋白包被的囊泡中蛋白质和膜的去除。在适当的刺激下，所得的成熟SG经历Ca 2+依赖性胞吐作用。我们在这里表明，马达蛋白肌球蛋白Va是有牵连的成熟步骤的SGs，它们的结合F-肌动蛋白和它们的刺激胞吐。肌球蛋白Va功能的干扰阻止了跨膜蛋白弗林蛋白酶从成熟的SG中的去除，而不影响SG腔蛋白质的浓缩和加工。此外，ATP抑制结合的SGs的F-肌动蛋白减少与渐进成熟和干扰后，肌球蛋白Va功能。此外，显性负性肌球蛋白Va尾或基于shRNA的肌球蛋白Va下调的表达干扰了SG的刺激胞吐。总之，我们的数据表明，肌球蛋白Va在成熟过程中的膜重塑的SGs的一个重要功能，并在他们的胞吐作用。
Hormone- and neuropeptide-containing secretory granules (SGs) of neuroendocrine PC12 cells are formed at the trans- Golgi network as immature SGs. These intermediates are converted to mature SGs in a complex maturation process, including matrix condensation, processing of cargo proteins and removal of proteins and membrane in clathrin-coated vesicles. The resulting mature SGs undergo Ca2+-dependent exocytosis upon an appropriate stimulus. We here show that the motor protein myosin Va is implicated in a maturation step of SGs, their binding to F-actin and their stimulated exocytosis. Interference with myosin Va function blocked the removal of the transmembrane protein furin from maturing SGs without affecting condensation and processing of proteins of the SG lumen. Furthermore, the ATP-inhibited binding of SGs to F-actin decreased with progressive maturation and upon interference with myosin Va function. Moreover, the expression of a dominant-negative myosin Va-tail or shRNA-based downregulation of myosin Va interfered with stimulated exocytosis of SGs. In summary, our data suggest an essential function of myosin Va in the membrane remodeling of SGs during maturation and a role in their exocytosis.