Delineating cooperative responses of processive motors in living cells

Artem K. Efremov, Anand Radhakrishnan, David S. Tsao, Carol S. Bookwalter, Kathleen M. Trybus, Michael R. Diehl*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    35 Scopus citations

    Abstract

    Characterizing the collective functions of cytoskeletal motors is critical to understanding mechanisms that regulate the internal organization of eukaryotic cells as well as the roles various transport defects play in human diseases. Though in vitro assays using synthetic motor complexes have generated important insights, dissecting collective motor functions within living cells still remains challenging. Here, we show that the protein heterodimerization switches FKBP-rapalog-FRB can be harnessed in engineered COS-7 cells to compare the collective responses of kinesin-1 and myosinVa motors to changes in motor number and cargo size. The dependence of cargo velocities, travel distances, and position noise on these parameters suggests that multiple myosinVa motors can cooperate more productively than collections of kinesins in COS-7 cells. In contrast to observations with kinesin-1 motors, the velocities and run lengths of peroxisomes driven by multiple myosinVa motors are found to increase with increasing motor density, but are relatively insensitive to the higher loads associated with transporting large peroxisomes in the viscoelastic environment of the COS-7 cell cytoplasm. Moreover, these distinctions appear to be derived from the different sensitivities of kinesin-1 and myosinVa velocities and detachment rates to forces at the single-motor level. The collective behaviors of certain processive motors, like myosinVa, may therefore be more readily tunable and have more substantial roles in intracellular transport regulatory mechanisms compared with those of other cytoskeletal motors.

    Original languageEnglish (US)
    Pages (from-to)E334-E343
    JournalPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Volume111
    Issue number3
    DOIs
    StatePublished - Jan 21 2014

    Keywords

    • Cooperativity
    • Intracellular transport
    • Microrheology
    • Motor proteins
    • Synthetic biology

    ASJC Scopus subject areas

    • General

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