Actin Dynamics Drive Microvillar Motility and Clustering during Brush Border Assembly

Dev Cell. 2019 Sep 9;50(5):545-556.e4. doi: 10.1016/j.devcel.2019.07.008. Epub 2019 Aug 1.

Abstract

Transporting epithelial cells generate arrays of microvilli, known as a brush border, to enhance functional capacity. To understand brush border formation, we used live cell imaging to visualize apical remodeling early in this process. Strikingly, we found that individual microvilli exhibit persistent active motility, translocating across the cell surface at ∼0.2 μm/min. Perturbation with inhibitors and photokinetic experiments revealed that microvillar motility is driven by actin assembly at the barbed ends of core bundles, which in turn is linked to robust treadmilling of these structures. Actin regulatory factors IRTKS and EPS8 localize to the barbed ends of motile microvilli, where they control the kinetics and nature of movement. As the apical surface of differentiating epithelial cells is crowded with nascent microvilli, persistent motility promotes collisions between protrusions and ultimately clustering and consolidation into higher-order arrays. Thus, microvillar motility represents a previously unrecognized driving force for apical surface remodeling and maturation during epithelial differentiation.

Keywords: adhesion; bundle; epithelium; protocadherin; treadmilling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Caco-2 Cells
  • Cadherins / metabolism
  • Cell Differentiation*
  • Cell Movement
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • HEK293 Cells
  • Humans
  • Microfilament Proteins / metabolism
  • Microvilli / metabolism*
  • Myosins / metabolism
  • Swine

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • BAIAP2L1 protein, human
  • Cadherins
  • EPS8 protein, human
  • Microfilament Proteins
  • Myosins