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Cited by 108Cellular Mechanics and InteractionsSkin and Cellular Biology ResearchMicrotubule and mitosis dynamics

Mechanoaccumulative Elements of the Mammalian Actin Cytoskeleton

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Schiffhauer, Eric S., Luo, Tianzhi, Mohan, Krithika, Srivastava, Vasudha, Qian, Xuyu, Griffis, Eric R., Iglesias, Pablo A., Robinson, Douglas N.·2016·Current Biology
DOI 10.1016/j.cub.2016.04.007PMC PMC4899209
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Abstract

To change shape, divide, form junctions, and migrate, cells reorganize their cytoskeletons in response to changing mechanical environments [1-4]. Actin cytoskeletal elements, including myosin II motors and actin crosslinkers, structurally remodel and activate signaling pathways in response to imposed stresses [5-9]. Recent studies demonstrate the importance of force-dependent structural rearrangement of α-catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11]. However, the complete landscape of cytoskeletal mechanoresponsive proteins and the mechanisms by which these elements sense and respond to force remain to be elucidated. To find mechanosensitive elements in mammalian cells, we examined protein relocalization in response to controlled external stresses applied to individual cells. Here, we show that non-muscle myosin II, α-actinin, and filamin accumulate to mechanically stressed regions in cells from diverse lineages. Using reaction-diffusion models for force-sensitive binding, we successfully predicted which mammalian α-actinin and filamin paralogs would be mechanoaccumulative. Furthermore, a "Goldilocks zone" must exist for each protein where the actin-binding affinity must be optimal for accumulation. In addition, we leveraged genetic mutants to gain a molecular understanding of the mechanisms of α-actinin and filamin catch-bonding behavior. Two distinct modes of mechanoaccumulation can be observed: a fast, diffusion-based accumulation and a slower, myosin II-dependent cortical flow phase that acts on proteins with specific binding lifetimes. Finally, we uncovered cell-type- and cell-cycle-stage-specific control of the mechanosensation of myosin IIB, but not myosin IIA or IIC. Overall, these mechanoaccumulative mechanisms drive the cell's response to physical perturbation during proper tissue development and disease.

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  • The presence of F-actin in such artificially-formed active zones may reflect cytoskeletal response due to changes in cortical tension, since a bead is much stiffer than a postsynaptic terminal.

    “The presence of F-actin in such artificially-formed active zones may reflect cytoskeletal response due to changes in cortical tension, since a bead is much stiffer than a postsynaptic terminal82.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [82]

    The Results and Discussion (page unavailable) show that actin-binding proteins accumulate in mechanically stressed regions of mammalian cells, supporting the proposed cytoskeletal response in general. The paper does not examine artificially formed active zones, compare bead stiffness with postsynaptic terminals, or establish that cortical-tension changes explain F-actin at those zones. (LLM, conf=0.84)

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Authors
Schiffhauer, E. S., Luo, T., Mohan, K., Srivastava, V., Qian, X., Griffis, E. R., Iglesias, P. A., & Robinson, D. N.
Affiliations
  • Johns Hopkins University (US)
  • University of Dundee (GB)
Corresponding author
Robinson, Douglas N.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2016-06
Volume
26
Issue
11
Pages
1473-1479
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2016.04.007
PMC
PMC4899209
OpenAlex
W2362157078
Cited by
108
References
0
Citations by year
2026: 10 · 2025: 9 · 2024: 8 · 2023: 7 · 2022: 15 · 2021: 10 · 2020: 14 · 2019: 12 · 2018: 10 · 2017: 10 · 2016: 3
FWCI
8.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Wellcome Trust (090064/Z/09/Z)
  • National Institutes of Health (1s10od016374-01, GM66817, GM086704)
  • National Institute of General Medical Sciences (R01GM086704, T32GM007445, R01GM109863, R01GM066817)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
actin cytoskeleton, mechanosensing, non-muscle myosin II, alpha-actinin, filamin, reaction-diffusion systems, myosin IIB, cell mechanics, protein relocalization, cortical flow, cell cycle
MeSH terms
Actinin, Animals, HeLa Cells, Humans, Actin Cytoskeleton, Myosin Type II, NIH 3T3 Cells, Mice, HEK293 Cells, Filamins

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