Carlsson Fredric, Stålhammar-Carlemalm Margaretha, Flärdh Klas, Sandin Charlotta, Carlemalm Eric, Lindahl Gunnar
Department of Laboratory Medicine, Lund University, SE-22362 Lund, Sweden.
Nature. 2006 Aug 24;442(7105):943-6. doi: 10.1038/nature05021.
All living cells require specific mechanisms that target proteins to the cell surface. In eukaryotes, the first part of this process involves recognition in the endoplasmic reticulum of amino-terminal signal sequences and translocation through Sec translocons, whereas subsequent targeting to different surface locations is promoted by internal sorting signals. In bacteria, N-terminal signal sequences promote translocation across the cytoplasmic membrane, which surrounds the entire cell, but some proteins are nevertheless secreted in one part of the cell by poorly understood mechanisms. Here we analyse localized secretion in the Gram-positive pathogen Streptococcus pyogenes, and show that the signal sequences of two surface proteins, M protein and protein F (PrtF), direct secretion to different subcellular regions. The signal sequence of M protein promotes secretion at the division septum, whereas that of PrtF preferentially promotes secretion at the old pole. Our work therefore shows that a signal sequence may contain information that directs the secretion of a protein to one subcellular region, in addition to its classical role in promoting secretion. This finding identifies a new level of complexity in protein translocation and emphasizes the potential of bacterial systems for the analysis of fundamental cell-biological problems.
所有活细胞都需要特定机制将蛋白质靶向运输到细胞表面。在真核生物中，这一过程的第一步涉及在内质网中识别氨基末端信号序列，并通过Sec转运体进行转运，而随后通过内部分选信号促进蛋白质靶向不同的表面位置。在细菌中，N末端信号序列促进蛋白质穿过围绕整个细胞的细胞质膜进行转运，但仍有一些蛋白质通过人们知之甚少的机制在细胞的某一部分分泌。在这里，我们分析了革兰氏阳性病原体化脓性链球菌中的局部分泌情况，并表明两种表面蛋白M蛋白和F蛋白（PrtF）的信号序列将分泌导向不同的亚细胞区域。M蛋白的信号序列促进在分裂隔膜处的分泌，而PrtF的信号序列则优先促进在旧极处的分泌。因此，我们的研究表明，信号序列除了在促进分泌方面的经典作用外，可能还包含将蛋白质分泌导向一个亚细胞区域的信息。这一发现揭示了蛋白质转运过程中一个新的复杂层面，并强调了细菌系统在分析基本细胞生物学问题方面的潜力。
