Molecular crowding creates traffic jams of kinesin motors on microtubules

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Despite the crowdedness of the interior of cells, microtubule-based motor proteins are able to deliver cargoes rapidly and reliably throughout the cytoplasm. We hypothesize that motor proteins may be adapted to operate in crowded environments by having molecular properties that prevent them from forming traffic jams. To test this hypothesis, we reconstituted high-density traffic of purified kinesin-8 motor protein, a highly processive motor with long end-residency time, along microtubules in a total internal-reflection fluorescence microscopy assay. We found that traffic jams, characterized by an abrupt increase in the density of motors with an associated abrupt decrease in motor speed, form even in the absence of other obstructing proteins. To determine the molecular properties that lead to jamming, we altered the concentration of motors, their processivity, and their rate of dissociation from microtubule ends. Traffic jams occurred when the motor density exceeded a critical value (density-induced jams) or when motor dissociation from the microtubule ends was so slow that it resulted in a pileup (bottleneck-induced jams). Through comparison of our experimental results with theoretical models and stochastic simulations, we characterized in detail under which conditions density- and bottleneck-induced traffic jams form or do not form. Our results indicate that transport kinesins, such as kinesin-1, may be evolutionarily adapted to avoid the formation of traffic jams by moving only with moderate processivity and dissociating rapidly from microtubule ends.

Details

Original languageEnglish
Pages (from-to)6100-6105
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Volume109
Issue number16
Publication statusPublished - 17 Apr 2012
Peer-reviewedYes

External IDs

PubMed 22431622
PubMedCentral PMC3341076
Scopus 84859933274
ORCID /0000-0002-0750-8515/work/142235547

Keywords

Research priority areas of TU Dresden

Keywords

  • Algorithms, Biological Transport, Green Fluorescent Proteins/genetics, Kinesins/genetics, Luminescent Proteins/genetics, Microscopy, Fluorescence/methods, Microtubules/metabolism, Models, Biological, Molecular Dynamics Simulation, Recombinant Fusion Proteins/genetics, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae Proteins/genetics