Actin filaments and microtubules create diverse cellular protrusions, but intermediate filaments, the strongest and most stable cytoskeletal elements, are not known to directly participate in the formation of protrusions. Here we show that keratin intermediate filaments directly regulate the morphogenesis of microridges, elongated protrusions arranged in elaborate maze-like patterns on the surface of mucosal epithelial cells. We found that microridges on zebrafish skin cells contained both actin and keratin filaments. Keratin filaments stabilized microridges, and overexpressing keratins lengthened them. Envoplakin and Periplakin, Plakin family cytolinkers that bind F-actin and keratins, localized to microridges and were required for their morphogenesis. Strikingly, Plakin protein levels directly dictated microridge length. An actin-binding domain of Periplakin was required to initiate microridge morphogenesis, whereas Periplakin-keratin binding was required to elongate microridges. These findings separate microridge morphogenesis into distinct steps, expand our understanding of intermediate filament functions, and identify microridges as protrusions that integrate actin and intermediate filaments.
- Alvaro Sagasti
- Alvaro Sagasti
- Aaron Paul van Loon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal experimental procedures were approved by the Chancellor's Animal Research Care Committee at UCLA (protocol #2005-117-41D).
- Michel Bagnat, Duke University, United States
- Received: April 22, 2020
- Accepted: September 4, 2020
- Accepted Manuscript published: September 7, 2020 (version 1)
© 2020, Inaba et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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