Desmoplakin assembly dynamics in four dimensions: Multiple phases differentially regulated by intermediate filaments and actin

Lisa M. Godsel, Sherry N. Hsieh, Evangeline V. Amargo, Amanda E. Bass, Lauren T. Pascoe-McGillicuddy, Arthur C. Huen, Meghan E. Thorne, Claire A. Gaudry, Jung K. Park, Kyunghee Myung, Robert D. Goldman, Teng Leong Chew, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

The intermediate filament (IF)-binding protein desmoplakin (DP) is essential for desmosome function and tissue integrity, but its role in junction assembly is poorly understood. Using time-lapse imaging, we show that cell-cell contact triggers three temporally overlapping phases of DP-GFP dynamics: (1) the de novo appearance of punctate fluorescence at new contact zones after as little as 3 min; (2) the coalescence of DP and the armadillo protein plakophilin 2 into discrete cytoplasmic particles after as little as 15 min; and (3) the cytochalasin-sensitive translocation of cytoplasmic particles to maturing borders, with kinetics ranging from 0.002 to 0.04 μm/s. DP mutants that abrogate or enhance association with IFs exhibit delayed incorporation into junctions, altering particle trajectory or increasing particle pause times, respectively. Our data are consistent with the idea that DP assembles into nascent junctions from both diffusible and particulate pools in a temporally overlapping series of events triggered by cell-cell contact and regulated by actin and DP-IF interactions.

Original languageEnglish (US)
Pages (from-to)1045-1059
Number of pages15
JournalJournal of Cell Biology
Volume171
Issue number6
DOIs
StatePublished - Dec 19 2005

ASJC Scopus subject areas

  • Cell Biology

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