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dc.contributor.authorHolcman, David
dc.contributor.authorParutto, Pierre
dc.contributor.authorChambers, Joseph
dc.contributor.authorFantham, Marcus
dc.contributor.authorYoung, Laurence
dc.contributor.authorMarciniak, Stefan
dc.contributor.authorKaminski, Clemens
dc.contributor.authorRon, David
dc.contributor.authorAvezov, Edward
dc.date.accessioned2018-11-16T00:31:23Z
dc.date.available2018-11-16T00:31:23Z
dc.date.issued2018-10
dc.identifier.issn1476-4679
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285153
dc.description.abstractThe endoplasmic reticulum (ER), a network of membranous sheets and pipes, supports functions encompassing biogenesis of secretory proteins and delivery of functional solutes throughout the cell[1, 2]. Molecular mobility through the ER network enables these functionalities, but diffusion alone is not sufficient to explain luminal transport across supramicrometre distances. Understanding the ER structure–function relationship is critical in light of mutations in ER morphology-regulating proteins that give rise to neurodegenerative disorders[3, 4]. Here, super-resolution microscopy and analysis of single particle trajectories of ER luminal proteins revealed that the topological organization of the ER correlates with distinct trafficking modes of its luminal content: with a dominant diffusive component in tubular junctions and a fast flow component in tubules. Particle trajectory orientations resolved over time revealed an alternating current of the ER contents, while fast ER super-resolution identified energy-dependent tubule contraction events at specific points as a plausible mechanism for generating active ER luminal flow. The discovery of active flow in the ER has implications for timely ER content distribution throughout the cell, particularly important for cells with extensive ER-containing projections such as neurons.
dc.description.sponsorshipWellcome Trust - 3-3249/Z/16/Z and 089703/Z/09/Z [Kaminski] UK Demential Research Institute [Avezov] Wellcome Trust - 200848/Z/16/Z, WT: UNS18966 [Ron] FRM Team Research Grant [Holcman] Engineering and Physical Sciences Research Council (EPSRC) - EP/L015889/1 and EP/H018301/1 [Kaminski] Medical Research Council (MRC) - MR/K015850/1 and MR/K02292X/1 [Kaminski]
dc.publisherSpringer Nature
dc.subjectCell Biology, Endoplasmic Reticulum, ER, Super resolution microscopy, Single Particle Tracking, Live Cell Imaging
dc.titleSingle particle trajectories reveal active endoplasmic reticulum luminal flow
dc.typeArticle
prism.endingPage1125
prism.publicationNameNature Cell Biology
prism.startingPage1118
prism.volume20
dc.identifier.doi10.17863/CAM.32523
dcterms.dateAccepted2018-08-09
rioxxterms.versionofrecord10.1038/s41556-018-0192-2
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08-09
dc.contributor.orcidChambers, Joseph [0000-0003-4675-0053]
dc.contributor.orcidFantham, Marcus [0000-0002-9921-3334]
dc.contributor.orcidMarciniak, Stefan [0000-0001-8472-7183]
dc.contributor.orcidKaminski, Clemens [0000-0002-5194-0962]
dc.contributor.orcidRon, David [0000-0002-3014-5636]
dc.contributor.orcidAvezov, Edward [0000-0002-2894-0585]
dc.identifier.eissn1476-4679
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (200848/Z/16/Z)
pubs.funder-project-idMedical Research Council (MR/K02292X/1)
pubs.funder-project-idMedical Research Council (G1002610)
pubs.funder-project-idAlpha One Foundation (unknown)
pubs.funder-project-idMedical Research Council (MR/R009120/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/H023917/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/H018301/1)
pubs.funder-project-idMedical Research Council (G0902243)
pubs.funder-project-idMedical Research Council (G0601840)
pubs.funder-project-idMedical Research Council (MR/K015850/1)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (089703/Z/09/Z)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/L015889/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/S009000/1)
cam.issuedOnline2018-09-17
rioxxterms.freetoread.startdate2019-03-17


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