Polarity protein Par3L deletion causes chromosomal segregation defects and tumorigenesis.

Apical-basal polarity is an intrinsic property of epithelial cells, which is governed by a set of conserved polarity proteins. Par3-like (Par3L), an ortholog of the classic polarity protein Par3, has been implicated in multiple diseases through genetic studies, but its biological functions are understudied. Here we found that Par3L deletion in mice lead to tumorigenesis in gastrointestinal track, prostates, and lungs. Par3L is also expressed in small subsets of cells in ovaries, testis, pancreas, brains, and kidneys, which did not show abnormal phenotypes in the Par3L KO mice. Further analysis of the gastrointestinal track in the Par3L KO mice found increased mitotic cells, which have significantly higher ratios of aberrant spindles compared to that of the WT mice. To delineate the potential mechanism, we tagged the endogenous Par3L coding sequence with a 3 x flag tag and identified the Par3L interacting proteins in intestine, kidneys, and pancreas. We found that Par3L interacts with proteins involved in chromatin remodeling and spindle assemblies, cytoskeleton and extracellular matrix, trafficking, metabolism, and mRNA processing. These data provide valuable information understanding the non-canonical polarity protein Par3L.