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Claudin‐4 promotes repair and barrier function in lung epithelia
Author(s) -
Rokkam Deepti,
Hirsch Jan,
Ho Gwen,
Griffin Chris,
LaFemina Michael J,
Frank James A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.865.6
Subject(s) - claudin , tight junction , lamellipodium , microbiology and biotechnology , barrier function , paracellular transport , gene knockdown , cell migration , chemistry , biology , cell , cell culture , biochemistry , genetics , membrane , permeability (electromagnetism)
Claudin‐4 is a transmembrane protein important in paracellular sealing at tight junctions. Recent studies have found that claudin‐4 is specifically induced during epithelial repair and higher claudin‐4 expression levels are associated with intact barrier function in injured human lungs. In this study, claudin‐4 expression and trafficking were examined in primary rat alveolar type 2 cells and human bronchial epithelial cells in a scratch wound migration assay. To determine the role of claudin‐4 in migration, cell morphology, actin distribution and focal adhesions were examined. To discover claudin‐4 binding partners, coimmunoprecipitates were evaluated by mass spectrometry. Induction of claudin‐4 during repair was conserved in alveolar and bronchial epithelia and knockdown of claudin‐4 slowed migration. EGFR and JNK signaling were required for claudin‐4 expression. During repair, claudin‐4 was trafficked to the leading edge of migrating cells where it appeared to influence actin nucleation and lamellipodia formation. Novel protein‐protein interactions with claudin‐4 may provide clues to the role of this protein in collective migration. The combined effects of claudin‐4 on tight junction sealing and epithelial repair potentially explain the positive correlation between claudin‐4 expression levels and epithelial barrier function in human lungs. Funded by NIH/NHLBI HL88440, HL88440S2