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Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes

Sanghavi, Paulomi ; D’Souza, Ashwin ; Rai, Ashim ; Rai, Arpan ; Padinhatheeri, Ranjith ; Mallik, Roop

Current biology, 2018-05, Vol.28 (9), p.1460-1466.e4 [Periódico revisado por pares]

England: Elsevier Inc

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  • Título:
    Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes
  • Autor: Sanghavi, Paulomi ; D’Souza, Ashwin ; Rai, Ashim ; Rai, Arpan ; Padinhatheeri, Ranjith ; Mallik, Roop
  • Assuntos: bidirectional transport ; Biological Transport ; Cell Line ; Dictyostelium ; dynein ; Dyneins - metabolism ; Dyneins - physiology ; intracellular transport ; kinesin ; Kinesins - metabolism ; Kinesins - physiology ; Markov process ; Microtubules - physiology ; Models, Biological ; optical trapping ; Phagocytosis ; Phagosomes - metabolism ; Phagosomes - physiology ; Probability ; Protein Transport - physiology ; vesicle transport
  • É parte de: Current biology, 2018-05, Vol.28 (9), p.1460-1466.e4
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
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    These authors contributed equally
  • Descrição: How the opposing activity of kinesin and dynein motors generates polarized distribution of organelles inside cells is poorly understood and hotly debated [1, 2]. Possible explanations include stochastic mechanical competition [3, 4], coordinated regulation by motor-associated proteins [5–7], mechanical activation of motors [8], and lipid-induced organization [9]. Here, we address this question by using phagocytosed latex beads to generate early phagosomes (EPs) that move bidirectionally along microtubules (MTs) in an in vitro assay [9]. Dynein/kinesin activity on individual EPs is recorded as real-time force generation of the motors against an optical trap. Activity of one class of motors frequently coincides with, or is rapidly followed by opposite motors. This leads to frequent and rapid reversals of EPs in the trap. Remarkably, the choice between dynein and kinesin can be explained by the tossing of a coin. Opposing motors therefore appear to function stochastically and independently of each other, as also confirmed by observing no effect on kinesin function when dynein is inhibited on the EPs. A simple binomial probability calculation based on the geometry of EP-microtubule contact explains the observed activity of dynein and kinesin on phagosomes. This understanding of intracellular transport in terms of a hypothetical coin, if it holds true for other cargoes, provides a conceptual framework to explain the polarized localization of organelles inside cells. •Optical trapping data on phagosomes analyzed mathematically•Dynein and kinesin function stochastically and independently of each other•Choice between these motors can be explained by tossing of a hypothetical coin•Regulatory factors may generate polarized transport by biasing this coin Sanghavi et al. analyze optical trapping data on phagosomes to propose that sub-cellular localization of organelles inside cells can be understood in terms of a hypothetical coin toss that decides motor protein activity (dynein versus kinesin) on the phagosome.
  • Editor: England: Elsevier Inc
  • Idioma: Inglês

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