title: A membrane metalloprotease participates in the sequential degradation of a Caulobacter polarity determinant.
abstract: Caulobacter crescentus assembles many of its cellular machines at distinct times and locations during the cell cycle. PodJ provides the spatial cues for the biogenesis of several polar organelles, including the pili, adhesive holdfast and chemotactic apparatus, by recruiting structural and regulatory proteins, such as CpaE and PleC, to a specific cell pole. PodJ is a protein with a single transmembrane domain that exists in two forms, full-length (PodJL) and truncated (PodJS), each appearing during a specific time period of the cell cycle to control different aspects of polar organelle development. PodJL is synthesized in the early predivisional cell and is later proteolytically converted to PodJS. During the swarmer-to-stalked transition, PodJS must be degraded to preserve asymmetry in the next cell cycle. We found that MmpA facilitates the degradation of PodJS. MmpA belongs to the site-2 protease (S2P) family of membrane-embedded zinc metalloproteases, which includes SpoIVFB and YluC of Bacillus subtilis and YaeL of Escherichia coli. MmpA appears to cleave within or near the transmembrane segment of PodJS, releasing it into the cytoplasm for complete proteolysis. While PodJS has a specific temporal and spatial address, MmpA is present throughout the cell cycle; furthermore, periplasmic fusion to mRFP1 suggested that MmpA is uniformly distributed around the cell. We also determined that mmpA and yaeL can complement each other in C. crescentus and E. coli, indicating functional conservation. Thus, the sequential degradation of PodJ appears to involve regulated intramembrane proteolysis (Rip) by MmpA.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, 300 Beckman Center, 279 Campus Drive, Stanford, CA 94305-5329, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Chen
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Viollier
authors.forename: Lucy
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D016934:Caulobacter / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle; D016764:Cell Polarity / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D005816:Genetic Complementation Test; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; C120058:podj protein, Caulobacter crescentus; D045726:Metalloproteases