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Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size

Author

Listed:
  • Igor Kondrychyn

    (RIKEN Center for Biosystems Dynamics Research)

  • Douglas J. Kelly

    (RIKEN Center for Biosystems Dynamics Research)

  • Núria Taberner Carretero

    (RIKEN Center for Biosystems Dynamics Research)

  • Akane Nomori

    (RIKEN Center for Biosystems Dynamics Research)

  • Kagayaki Kato

    (National Institutes of Natural Sciences
    National Institutes of Natural Sciences)

  • Jeronica Chong

    (RIKEN Center for Biosystems Dynamics Research)

  • Hiroyuki Nakajima

    (National Cerebral and Cardiovascular Center, Research Institute)

  • Satoru Okuda

    (WPI Nano Life Science Institute, Kanazawa University)

  • Naoki Mochizuki

    (National Cerebral and Cardiovascular Center, Research Institute)

  • Li-Kun Phng

    (RIKEN Center for Biosystems Dynamics Research)

Abstract

The formation of vascular tubes is driven by extensive changes in endothelial cell (EC) shape. Here, we have identified a role of the actin-binding protein, Marcksl1, in modulating the mechanical properties of EC cortex to regulate cell shape and vessel structure during angiogenesis. Increasing and depleting Marcksl1 expression level in vivo results in an increase and decrease, respectively, in EC size and the diameter of microvessels. Furthermore, endothelial overexpression of Marcksl1 induces ectopic blebbing on both apical and basal membranes, during and after lumen formation, that is suppressed by reduced blood flow. High resolution imaging reveals that Marcksl1 promotes the formation of linear actin bundles and decreases actin density at the EC cortex. Our findings demonstrate that a balanced network of linear and branched actin at the EC cortex is essential in conferring cortical integrity to resist the deforming forces of blood flow to regulate vessel structure.

Suggested Citation

  • Igor Kondrychyn & Douglas J. Kelly & Núria Taberner Carretero & Akane Nomori & Kagayaki Kato & Jeronica Chong & Hiroyuki Nakajima & Satoru Okuda & Naoki Mochizuki & Li-Kun Phng, 2020. "Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19308-5
    DOI: 10.1038/s41467-020-19308-5
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    Cited by:

    1. Caitlin R. Francis & Hayle Kincross & Erich J. Kushner, 2022. "Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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