The Cpx stress response system of Escherichia coli senses plasma membrane proteins and controls HtpX, a membrane protease with a cytosolic active site.
BACKGROUND
The abnormal accumulation of misfolded proteins outside the plasma (cytoplasmic or inner) membrane up-regulates the synthesis of a class of envelope-localized catalysts of protein folding and degradation. The pathway for this transmembrane signalling is mediated by the CpxR-CpxA two-component phospho-relay mechanism.


RESULTS
We now show that an abnormality in the plasma membrane proteins, due either to the impairment of FtsH, a protease acting against integral membrane proteins, or to the overproduction of a substrate membrane protein of FtsH, activates this stress response pathway. Under such conditions, the cpxR gene function becomes essential for cell growth. We further show that the expression of a putative protease, HtpX, in the plasma membrane, is under the control of CpxR. Synthetic growth inhibition was observed when the ftsH and htpX disruption mutations had been combined, suggesting that these gene products have some complementary or overlapping proteolytic functions. Topology analyses indicated that the metalloproteinase active site of HtpX is located on the cytosolic side of the membrane.


CONCLUSIONS
Taken together, these results suggest that the Cpx "extracytoplasmic" stress response system controls the quality of the plasma membrane, even on its cytoplasmic side.
Shimohata
Nobuyuki
N
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Chiba
Shinobu
S
Saikawa
Naoya
N
Ito
Koreaki
K
Akiyama
Yoshinori
Y
D049069:ATP-Dependent Proteases; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000502:physiology*; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D045726:Metalloproteases
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; C112840:YccA protein, E coli; C068607:HtpX protein, E coli; C085504:CpxR protein, Bacteria; D045726:Metalloproteases; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; D008666:Metalloendopeptidases