Mol Biol Cell. 2021 Oct 01;32(20):ar2. doi: 10.1091/mbc.E21-02-0087. Epub 2021 Jul 28.

Roles for Ndel1 in keratin organization and desmosome function.

Molecular biology of the cell

Yong-Bae Kim, Daniel Hlavaty, Jeff Maycock, Terry Lechler

PMID: 34319758 DOI: 10.1091/mbc.E21-02-0087

Abstract

Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell-cell adhesion complexes that provide essential mechanical integrity to this tissue. Despite this, we know little about how keratin organization is controlled and whether desmosomes locally regulate keratin dynamics in addition to binding preassembled filaments. Ndel1 is a desmosome-associated protein in the differentiated epidermis, though its function at these structures has not been examined. Here, we show that Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins. Further, Ndel1 was necessary for robust desmosome-keratin association and sufficient to reorganize keratins at distinct cellular sites. Lis1, a Ndel1 binding protein, was required for desmosomal localization of Ndel1, but not for its effects on keratin filaments. Finally, we use mouse genetics to demonstrate that loss of Ndel1 results in desmosome defects in the epidermis. Our data thus identify Ndel1 as a desmosome-associated protein that promotes local assembly/reorganization of keratin filaments and is essential for robust desmosome formation.

Publication Types

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

Grant support

• R01 AR055926/AR/NIAMS NIH HHS/United States
• R01 AR067203/AR/NIAMS NIH HHS/United States