Characterization of human thioredoxin-like 2: A novel microtubule-binding thioredoxin expressed predominantly in the cilia of lung airway epithelium and spermatid manchette and axoneme

Christine M. Sadek, Alberto Jiménez, Anastasios E. Damdimopoulos, Thomas Kieselbach, Magnus Nord, Jan Åke Gustafsson, Giannis Spyrou, Elaine C. Davis, Richard Oko, Frans A. Van der Hoorn, Antonio Miranda-Vizuete

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

We describe here the cloning and characterization of a novel member of the thioredoxin family, thioredoxin-like protein 2 (Txl-2). The Txl-2 open reading frame codes for a protein of 330 amino acids consisting of two distinct domains: an N-terminal domain typical of thioredoxins and a C-terminal domain belonging to the nucleoside-diphosphate kinase family, separated by a small interface domain. The Txl-2 gene spans ∼28 kb, is organized into 11 exons, and maps at locus 3q22.3-q23. A splicing variant lacking exon 5 (Δ5Txl-2) has also been isolated. By quantitative real time PCR we demonstrate that Txl-2 mRNA is ubiquitously expressed, with testis and lung having the highest levels of expression. Unexpectedly, light and electron microscopy analyses show that the protein is associated with microtubular structures such as lung airway epithelium cilia and the manchette and axoneme of spermatids. Using in vitro translated proteins, we demonstrate that full-length Txl-2 weakly associates with microtubules. In contrast, Δ5Txl-2 specifically binds with very high affinity brain microtubule preparations containing microtubule-binding proteins. Importantly, Δ5Txl-2 also binds to pure microtubules, proving that it possesses intrinsic microtubule binding capability. Taken together, Δ5Txl-2 is the first thioredoxin reported to bind microtubules and might therefore be a novel regulator of microtubule physiology.

Original languageEnglish (US)
Pages (from-to)13133-13142
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number15
DOIs
StatePublished - Apr 11 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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