AI Article Synopsis

  • A single epithelial cell can divide and form a cyst, a key step in organ development; however, it starts with a temporary "inverted" polarity between the cell's membranes.
  • For proper cyst formation, cells must reorient their polarity, which involves the internalization of apical proteins and their transport to the area where cells connect, forming a lumen.
  • The proteins Rac1 and IQGAP1, activated by signals from the extracellular matrix, are crucial for this reorientation process, as they work together to promote endocytosis of apical proteins in epithelial cells during the two-cell stage.

Article Abstract

A single epithelial cell embedded in extracellular matrix (ECM) can proliferate to form an apical lumen-harboring cyst, whose formation is a fundamental step in epithelial organ development. At an early two-cell stage after cell division, the cell doublet typically displays "inverted" polarity, with apical and basolateral proteins being located to the ECM-facing and cell-cell-contacting plasma membranes, respectively. Correct cystogenesis requires polarity reorientation, a process containing apical protein endocytosis from the ECM-abutting periphery and subsequent apical vesicle delivery to a cell-cell contact site for lumen formation. Here, we show that downstream of the ECM-signal-transducer β1-integrin, Rac1, and its effector IQGAP1 promote apical protein endocytosis, contributing to polarity reorientation of mammalian epithelial Madin-Darby canine kidney (MDCK) cells at a later two-cell stage in three-dimensional culture. Rac1-GTP facilitates IQGAP1 interaction with the Rac-specific activator Tiam1, which also contributes to the endocytosis and enhances the effect of IQGAP1. These findings suggest that Tiam1 and IQGAP1 form a positive feedback loop to activate Rac1. With Rac1-GTP, IQGAP1 also binds to AP2α, an adaptor protein subunit for clathrin-mediated endocytosis; depletion of the AP2 complex impairs apical protein endocytosis in MDCK doublets. Thus, Rac1 likely participates in polarity reorientation at the two-cell stage via its interaction with IQGAP1.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609601PMC
http://dx.doi.org/10.1111/gtc.13169DOI Listing

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