The POF1B candidate gene for premature ovarian failure regulates epithelial polarity

Valeria Padovano, Ilaria Lucibello, Valentina Alari, Pamela Della Mina, Arianna Crespi, Ilaria Ferrari, Marta Recagni, Donatella Lattuada, Marco Righi, Daniela Toniolo, Antonello Villa, Grazia Pietrini

Research output: Contribution to journalArticle

Abstract

POF1B is a candidate gene for premature ovarian failure (POF); it is mainly expressed in polarised epithelial tissues, but its function in these tissues and the relationship with the disorder are unknown. Here we show colocalisation of POF1B with markers of both adherens and tight junctions in human jejunum. The tight junction localisation was maintained by the human POF1B stably expressed in the MDCK polarised epithelial cell line, whereas it was lost by the POF1B R329Q variant associated with POF. Localisation of apico-basal polarity markers and ultrastructure of the tight junctions were maintained in cells expressing the mutant. However, tight junction assembly was altered, cells were dysmorphic and the monolayer organisation was also altered in three-dimensional culture systems. Moreover, cells expressing the POF1B R329Q variant showed defects in ciliogenesis and cystogenesis as a result of misorientation of primary cilia and mitotic division. All of these defects were explained by interference of the mutant with the content and organisation of F-actin at the junctions. A role for POF1B in the regulation of the actin cytoskeleton was further verified by shRNA silencing of the endogenous protein in human intestinal Caco-2 cells. Taken together, these data indicate that localisation of POF1B to tight junctions has a key role in the organisation of epithelial monolayers by regulating the actin cytoskeleton.

Original languageEnglish
Pages (from-to)3356-3368
Number of pages13
JournalJournal of Cell Science
Volume124
Issue number19
DOIs
Publication statusPublished - Oct 1 2011

Keywords

  • 3D multi-lumen cyst
  • Cell shape
  • Epithelial polarity
  • F-actin
  • POF1B shRNA
  • Primary cilia
  • Tight junctions

ASJC Scopus subject areas

  • Cell Biology

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