title: Regulated intramembrane proteolysis of FtsL protein and the control of cell division in Bacillus subtilis.
abstract: The small bitopic division protein FtsL is an essential part of the division machinery (divisome) in most eubacteria. In Bacillus subtilis FtsL is a highly unstable protein and the turnover has been implicated in regulation of division in response to DNA damage. N-terminal deletions and a domain swap experiment identified the short cytoplasmic domain of FtsL as being required for instability. We then identified a zinc metalloprotease, YluC, required for turnover, and likely sequence motifs involved in substrate recognition. YluC belongs to the site-2-protease (S2P) family of proteases involved in regulated intramembrane proteolysis (RIP), which plays a role in diverse regulatory phenomena from bacteria to man. The yluC mutant, and strains with N-terminal truncations of ftsL have a short cell phenotype, indicating that that FtsL is normally rate-limiting for division. Coexpression experiments of FtsL and YluC in Escherichia coli corroborated a model in which FtsL is directly cleaved by the membrane metalloprotease. The results shed new light on the regulation of cell division in B. subtilis and identify a novel class of targets for RIP.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Bramkamp
authors.forename: Louise
authors.initials: L
authors.lastname: Weston
authors.forename: Richard A
authors.initials: RA
authors.lastname: Daniel
authors.forename: Jeff
authors.initials: J
authors.lastname: Errington
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D045726:Metalloproteases / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D045726:Metalloproteases