Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components

Shinichiro Hanada, Masaru Harada, Hiroto Kumemura, M. Bishr Omary, Takumi Kawaguchi, Eitaro Taniguchi, Hironori Koga, Takafumi Yoshida, Michiko Maeyama, Shinji Baba, Takato Ueno, Michio Sata

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Many neurodegenerative diseases are characterized by the presence of protein aggregates bundled with intermediate filaments (IFs) and similar structures, known as Mallory bodies (MBs), are observed in various liver diseases. IFs are anchored at desmosomes and hemidesmosomes, however, interactions with other intercellular junctions have not been determined. We investigated the effect of IF inclusions on junction-associated and cytosolic proteins in various cultured cells. We performed gene transfection of the green fluorescent protein (GFP)-tagged cytokeratin (CK) 18 mutant arg89cys (GFP-CK18 R89C) in cultured cells and observed CK aggregations as well as loss of IF networks. Among various junction-associated proteins, zonula occludens-1 and β-catenin were colocalized with CK aggregates on immunofluorescent analyses. Similar results were obtained on immunostaining for cytosolic proteins, 14-3-3 ζ protein, glucose-6-phosphate dehydrogenase and DsRed. E-cadherin, a basolateral membrane protein in polarized epithelia, was present on both the apical and basolateral domains in GFP-CK18 R89C-transfected cells. Furthermore, cells containing CK aggregates were significantly larger than GFP-tagged wild type CK18 (GFP-WT CK18)-transfected or non-transfected cells (P < 0.01) and sometimes their morphology was significantly altered. Our data indicate that CK aggregates affect not only cell morphology but also the localization of various cytosolic components, which may affect the cellular function.

Original languageEnglish (US)
Pages (from-to)471-482
Number of pages12
JournalExperimental cell research
Volume304
Issue number2
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Aggresome
  • Cytokeratin
  • Mallory body
  • Proliferation

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