Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway.
Cell Mol Neurobiol. 2010 Nov;30(8):1303-8. doi: 10.1007/s10571-010-9597-6. Epub 2010 Nov 16.
Neuroendocrine secretory granules (SGs) are formed at the trans-Golgi network (TGN) as immature intermediates. In PC12 cells, these immature SGs (ISGs) are transported within seconds to the cell cortex, where they move along actin filaments and complete maturation. This maturation process comprises acidification-dependent processing of cargo proteins, condensation of the SG matrix, and removal of membrane and proteins not destined to mature SGs (MSGs) into ISG-derived vesicles (IDVs). We investigated the roles of myosin Va and Rab3 isoforms in the maturation of ISGs in neuroendocrine PC12 cells. The expression of dominant-negative mutants of myosin Va or Rab3D blocked the removal of the endoprotease furin from ISGs. Furthermore, expression of mutant Rab3D, but not of mutant myosin Va, impaired cargo processing of SGs. In conclusion, our data suggest an implication of myosin Va and Rab3D in the maturation of SGs where they participate in overlapping but not identical tasks.
神经内分泌分泌颗粒 (SGs) 作为不成熟的中间产物在跨高尔基网络 (TGN) 中形成。在 PC12 细胞中，这些不成熟的 SGs (ISGs) 在几秒钟内被运输到细胞皮层，在那里它们沿着肌动蛋白丝移动并完成成熟。这个成熟过程包括货物蛋白的酸化依赖性加工、SG 基质的浓缩，以及将膜和不会成熟成 MSG 的蛋白质（ISG 衍生的囊泡 IDVs）从 ISG 中去除。我们研究了肌球蛋白 Va 和 Rab3 同工型在神经内分泌 PC12 细胞中 ISG 成熟中的作用。肌球蛋白 Va 或 Rab3D 的显性失活突变体的表达阻断了内肽酶 furin 从 ISGs 中的去除。此外，突变 Rab3D 的表达，而不是突变肌球蛋白 Va 的表达，损害了 SG 的货物加工。总之，我们的数据表明肌球蛋白 Va 和 Rab3D 参与了 SG 的成熟，它们参与了重叠但不相同的任务。
