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Signal sequence directs localized secretion of bacterial surface proteins


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 signals1. 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 mechanisms2,3. 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 problems4.

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Figure 1: Surface distribution and secretion pattern for M6 and PrtF in S. pyogenes.
Figure 2: Domain swaps derived from M6 and PrtF are expressed on the streptococcal surface.
Figure 3: Signal sequences direct secretion to different subcellular regions.
Figure 4: Distribution of SecA in S. pyogenes.


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We thank A. Frigyesi for statistical analysis, L. Gefors for technical assistance, R. Freudl for anti-SecA antiserum, and E. Hanski, K. Pogliano and J. Scott for bacterial strains. This work was financed by the Swedish Research Council, Lund University Hospital, The Royal Physiographic Society in Lund, and the Trusts of Golje, Kock, Lundström and Österlund.

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Correspondence to Gunnar Lindahl.

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Carlsson, F., Stålhammar-Carlemalm, M., Flärdh, K. et al. Signal sequence directs localized secretion of bacterial surface proteins. Nature 442, 943–946 (2006).

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