Abstract:
:Intracellular transport is interspersed with frequent reversals in direction due to the presence of opposing kinesin and dynein motors on organelles that are carried as cargo. The cause and the mechanism of reversals are unknown, but are a key to understanding how cargos are delivered in a regulated manner to specific cellular locations. Unlike established single-motor biophysical assays, this problem requires understanding of the cooperative behavior of multiple interacting motors. Here we present measurements inside live Dictyostelium cells, in a cell extract and with purified motors to quantify such an ensemble function of motors. We show through precise motion analysis that reversals during endosome motion are caused by a tug-of-war between kinesin and dynein. Further, we use a combination of optical trap-based force measurements and Monte Carlo simulations to make the surprising discovery that endosome transport uses many (approximately four to eight) weak and detachment-prone dyneins in a tug-of-war against a single strong and tenacious kinesin. We elucidate how this clever choice of dissimilar motors and motor teams achieves net transport together with endosome fission, both of which are important in controlling the balance of endocytic sorting. To the best of our knowledge, this is a unique demonstration that dynein and kinesin function differently at the molecular level inside cells and of how this difference is used in a specific cellular process, namely endosome biogenesis. Our work may provide a platform to understand intracellular transport of a variety of organelles in terms of measurable quantities.
journal_name
Proc Natl Acad Sci U S Aauthors
Soppina V,Rai AK,Ramaiya AJ,Barak P,Mallik Rdoi
10.1073/pnas.0906524106subject
Has Abstractpub_date
2009-11-17 00:00:00pages
19381-6issue
46eissn
0027-8424issn
1091-6490pii
0906524106journal_volume
106pub_type
杂志文章abstract::A mutation in RPB5 (rpb5-9), an essential RNA polymerase subunit assembled into RNA polymerases I, II, and III, revealed a role for this subunit in transcriptional activation. Activation by GAL4-VP16 was impaired upon in vitro transcription with mutant whole-cell extracts. In vivo experiments using inducible reporter ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.26.15281
更新日期:1998-12-22 00:00:00
abstract::Terrestrial solar UVB radiation ( approximately 295-320 nm) readily induces cyclobutane pyrimidine dimers (CPDs) in human skin DNA that result in characteristic mutations associated with nonmelanoma skin cancer. The proinflammatory cytokine TNFalpha is important in mouse skin chemical carcinogenesis and is thought to ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0703385104
更新日期:2007-11-27 00:00:00
abstract::VIP21/caveolin is localized to both caveolae and apical transport vesicles and presumably cycles between the cell surface and the Golgi complex. We have studied the lipid interactions of this protein by reconstituting Escherichia coli-expressed VIP21/caveolin into liposomes. Surprisingly, the protein reconstituted onl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.22.10339
更新日期:1995-10-24 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1805802115
更新日期:2018-06-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611508104
更新日期:2007-08-14 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.9.3948
更新日期:1995-04-25 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.16.7749
更新日期:1993-08-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2016-06-07 00:00:00
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更新日期:1996-08-06 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2018-04-24 00:00:00
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pub_type: 杂志文章
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更新日期:2012-11-27 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2012-10-02 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-09-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1982-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-06-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1982-06-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1972-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2013-05-14 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2000-04-25 00:00:00
abstract::Discrete state models are a common tool of modeling in many areas. E.g., Markov state models as a particular representative of this model family became one of the major instruments for analysis and understanding of processes in molecular dynamics (MD). Here we extend the scope of discrete state models to the case of s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2014-10-14 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2001-03-13 00:00:00