Dynamical Localization of DivL and PleC in the Asymmetric Division Cycle of Caulobacter crescentus: A Theoretical Investigation of Alternative Models

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dc.contributor.authorSubramanian, Kartiken
dc.contributor.authorPaul, Mark R.en
dc.contributor.authorTyson, John J.en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2016-12-09T21:28:35Zen
dc.date.available2016-12-09T21:28:35Zen
dc.date.issued2015-07-01en
dc.description.abstractCell-fate asymmetry in the predivisional cell of Caulobacter crescentus requires that the regulatory protein DivL localizes to the new pole of the cell where it up-regulates CckA kinase, resulting in a gradient of CtrA~P across the cell. In the preceding stage of the cell cycle (the “stalked” cell), DivL is localized uniformly along the cell membrane and maintained in an inactive form by DivK~P. It is unclear how DivL overcomes inhibition by DivK~P in the predivisional cell simply by changing its location to the new pole. It has been suggested that co-localization of DivL with PleC phosphatase at the new pole is essential to DivL’s activity there. However, there are contrasting views on whether the bifunctional enzyme, PleC, acts as a kinase or phosphatase at the new pole. To explore these ambiguities, we formulated a mathematical model of the spatiotemporal distributions of DivL, PleC and associated proteins (DivJ, DivK, CckA, and CtrA) during the asymmetric division cycle of a Caulobacter cell. By varying localization profiles of DivL and PleC in our model, we show how the physiologically observed spatial distributions of these proteins are essential for the transition from a stalked cell to a predivisional cell. Our simulations suggest that PleC is a kinase in predivisional cells, and that, by sequestering DivK~P, the kinase form of PleC enables DivL to be reactivated at the new pole. Hence, co-localization of PleC kinase and DivL is essential to establishing cellular asymmetry. Our simulations reproduce the experimentally observed spatial distribution and phosphorylation status of CtrA in wild-type and mutant cells. Based on the model, we explore novel combinations of mutant alleles, making predictions that can be tested experimentally.en
dc.description.versionPublished versionen
dc.format.extent? - ? (27) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1004348en
dc.identifier.issn1553-734Xen
dc.identifier.issue7en
dc.identifier.urihttp://hdl.handle.net/10919/73620en
dc.identifier.volume11en
dc.languageEnglishen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000360620100022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBiochemical Research Methodsen
dc.subjectMathematical & Computational Biologyen
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectBACTERIAL-CELL-CYCLEen
dc.subjectPOLAR LOCALIZATIONen
dc.subjectRESPONSE REGULATORen
dc.subjectDNA-REPLICATIONen
dc.subjectHISTIDINE KINASEen
dc.subjectTEMPORAL CONTROLen
dc.subjectSINORHIZOBIUM-MELILOTIen
dc.subjectCHROMOSOME SEGREGATIONen
dc.subjectALPHA-PROTEOBACTERIAen
dc.subjectPROTEIN LOCALIZATIONen
dc.titleDynamical Localization of DivL and PleC in the Asymmetric Division Cycle of Caulobacter crescentus: A Theoretical Investigation of Alternative Modelsen
dc.title.serialPLOS Computational Biologyen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Distinguished Professorsen

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