Distinct activities of Scrib module proteins organize epithelial polarity

To enable their physiological functions, cells must polarize their plasma membrane. In many epithelia, polarity is regulated by balanced activity of the apical Par complex and basolateral Scribble module. While the former is understood in molecular detail, little is known about how the latter works. We identify distinct functions of the three Scribble module proteins, separating independent roles in a localization hierarchy from cooperative roles in apical polarity antagonism, and showing that they are not together sufficient to specify basolateral identity. This work establishes an essential basis for a mechanistic understanding of this core polarity machinery that controls processes ranging from stem cell divisions to organ morphogenesis across animal species.