The matrix protein of Marburg virus is transported to the plasma membrane along cellular membranes:: Exploiting the retrograde late endosomal pathway
The matrix protein of Marburg virus is transported to the plasma membrane along cellular membranes:: Exploiting the retrograde late endosomal pathway
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DOI：
10.1128/jvi.78.5.2382-2393.2004
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Becker, S
中科院分区：
文献类型：
--
作者：
Kolesnikova, L;Bamberg, S;Becker, S
VP 40是马尔堡病毒的基质蛋白，是一种外周膜蛋白，已显示其与多泡体（MVB）的膜结合（L. Koleskova，H. Bugany，H.- D. Klenk和S. Becker，J. Virol. 76：1825-1838，2002）。目前的研究表明，VP 40在合成后迅速结合到细胞膜上。进行时程研究以追踪表达过程中VP 40的分布。首先，VP 40均匀分布在整个细胞质中，尽管大多数蛋白质（70%）已经与膜结合。接着，VP 40在MVB和从MVB出现的管状突起中积累。最后，VP 40在质膜下以斑块状出现。碘克沙醇密度梯度分析支持这些形态学结果。大多数VP 40阳性膜首先检测到与小囊泡共迁移。然后将VP 40转移至含有内体标记蛋白的级分，随后转移至含有质膜标记蛋白的级分。阻断蛋白质合成的时候，使用放线菌酮时，VP 40主要是与小泡没有阻止VP 40的再分配到晚期内体，并进一步质膜。莫能菌素对胞内囊泡运输的抑制显著减少了VP 40在质膜上的出现。总之，我们认为，运输的马尔堡病毒基质蛋白VP 40涉及它的，积累在MVBs的VP 40富集膜簇的再分配到质膜。
VP40, the matrix protein of Marburg virus, is a peripheral membrane protein that has been shown to associate with membranes of multivesicular bodies (MVBs) (L. Kolesnikova, H. Bugany, H.-D. Klenk, and S. Becker, J. Virol. 76:1825-1838, 2002). The present study revealed that VP40 is bound to cellular membranes rapidly after synthesis. Time course studies were performed to trace the distribution of VP40 during the course of expression. First, VP40 was homogenously distributed throughout the cytoplasm, although the majority of protein (70%) was already membrane associated. Next, VP40 accumulated in MVBs and in tubular protrusions emerging from MVBs. Finally, VP40 appeared in a patch-like pattern beneath the plasma membrane. These morphological results were supported by iodixanol density gradient analyses. The majority of VP40-positive membranes were first detected comigrating with small vesicles. VP40 was then shifted to fractions containing endosomal marker proteins, and later, to fractions containing plasma membrane marker proteins. Blocking of protein synthesis by use of cycloheximide at the time when VP40 was mainly associated with the small vesicles did not prevent the redistribution of VP40 to the late endosomes and further to the plasma membrane. The inhibition of intracellular vesicular trafficking by monensin significantly reduced the appearance of VP40 at the plasma membrane. In conclusion, we suggest that the transport of the Marburg virus matrix protein VP40 involves its, accumulation in MVBs followed by the redistribution of VP40-enriched membrane clusters to the plasma membrane.