Tight Junction Component Occludin Binds to FIP5 to Regulate Endosome Trafficking and Mitotic Spindle Function

Area of Science:

• Evolutionary biology
• Cell biology
• Molecular biology

Background:

• The genetic underpinnings of vertebrate evolution remain largely unexplored.
• Vertebrate-specific genes, like Occludin (Ocln), are key to understanding this evolutionary transition.

Purpose of the Study:

• To investigate the role of Occludin (Ocln) in vertebrate development and cell function.
• To elucidate the molecular mechanisms by which Ocln influences cell division and tissue morphogenesis.

Main Methods:

• Analysis of mammary glands lacking Ocln in a mouse model.
• Investigation of Ocln's interaction with RabGTPase-11 adaptor FIP5.
• Microscopy to observe mitotic spindle orientation and cell division.

Main Results:

• Ocln deficiency in mammary glands led to impaired epithelial branching, reduced cell proliferation, and limited surface expansion.
• Ocln was found to regulate mitotic spindle orientation and function, with its absence causing prolonged prophase and division failures.
• Ocln interacts with FIP5, recruiting recycling endosomes to the centrosome for spindle assembly and function. FIP5 loss mimicked Ocln null phenotypes.

Conclusions:

• Occludin (Ocln) plays a novel role in endosomal trafficking, essential for spindle assembly and function.
• OCLN-mediated endosomal and membranous vesicle trafficking is evolutionarily conserved and vital for vertebrate development.