Smoothelin-like 2 Inhibits Coronin-1B to Stabilize the Apical Actin Cortex during Epithelial Morphogenesis.

Journal Article (Journal Article)

The actin cortex is involved in many biological processes and needs to be significantly remodeled during cell differentiation. Developing epithelial cells construct a dense apical actin cortex to carry out their barrier and exchange functions. The apical cortex assembles in response to three-dimensional (3D) extracellular cues, but the regulation of this process during epithelial morphogenesis remains unknown. Here, we describe the function of Smoothelin-like 2 (SMTNL2), a member of the smooth-muscle-related Smoothelin protein family, in apical cortex maturation. SMTNL2 is induced during development in multiple epithelial tissues and localizes to the apical and junctional actin cortex in intestinal and kidney epithelial cells. SMTNL2 deficiency leads to membrane herniations in the apical domain of epithelial cells, indicative of cortex abnormalities. We find that SMTNL2 binds to actin filaments and is required to slow down the turnover of apical actin. We also characterize the SMTNL2 proximal interactome and find that SMTNL2 executes its functions partly through inhibition of coronin-1B. Although coronin-1B-mediated actin dynamics are required for early morphogenesis, its sustained activity is detrimental for the mature apical shape. SMTNL2 binds to coronin-1B through its N-terminal coiled-coil region and negates its function to stabilize the apical cortex. In sum, our results unveil a mechanism for regulating actin dynamics during epithelial morphogenesis, providing critical insights on the developmental control of the cellular cortex.

Full Text

Duke Authors

Cited Authors

  • Hachimi, M; Grabowski, C; Campanario, S; Herranz, G; Baonza, G; Serrador, JM; Gomez-Lopez, S; Barea, MD; Bosch-Fortea, M; Gilmour, D; Bagnat, M; Rodriguez-Fraticelli, AE; Martin-Belmonte, F

Published Date

  • February 22, 2021

Published In

Volume / Issue

  • 31 / 4

Start / End Page

  • 696 - 706.e9

PubMed ID

  • 33275893

Pubmed Central ID

  • PMC8157312

Electronic International Standard Serial Number (EISSN)

  • 1879-0445

Digital Object Identifier (DOI)

  • 10.1016/j.cub.2020.11.010

Language

  • eng

Conference Location

  • England