The cell polarity protein scribble (SCRIB) has important functions in establishing apical-basal cell polarity during early development of multiple organs including the mammary gland. During pregnancy, mammary epithelial cells expand to develop lobuloalveolar structures containing apical-basal polarised epithelia that produce milk. It is unknown whether polarity proteins such as SCRIB regulate mammary epithelial alveologenesis. In their Short Report on page 2307, Senthil Muthuswamy and co-workers investigate the role of SCRIB during pregnancy by using an inducible RNA interference mouse model that they developed to knockdown SCRIB expression. They demonstrate that depletion of SCRIB in adult mice significantly inhibits lactogenic-hormone-induced mammary epithelial cell proliferation and alveologenesis. This phenotype is autonomous to the epithelial cells and was not impacted upon by the stroma. Mechanistically, lack of SCRIB downregulated the cell surface levels of the prolactin receptor, leading to its intracellular accumulation in Rab11-containing recycling endosomes. Consistent with a decrease in surface receptor levels, prolactin-induced JAK2–STAT5 signalling was significantly impaired in cells lacking SCRIB. Whereas previous studies have reported that SCRIB is a negative regulator of proliferation during early mammary development, the findings from the Muthuswamy laboratory identify a surprising role for SCRIB as a positive regulator of proliferation during pregnancy-induced alveologenesis.

• © 2016. Published by The Company of Biologists Ltd