Milk secretion by mammary glands is established at birth by a complex set of coordinated swithes, one of which involves the sealing of tight junctions between secretory epithelial cells. Now Andreas Fisher and co-workers report that the Rho effector protein PKN1 (protein kinase N1) is an important player in the process (see ). By making transgenic mice that express constitutively active PKN1 in the mammary epithelium, the authors show that, although the mammary glands of these mice develop normally during pregnancy, the mice lactate poorly and their glands involute soon after parturition. By injecting radioactive sucrose intraductally, the authors demonstrate that the epithelial tight junctions in the lactating transgenic glands are poorly sealed. Also, by analysing mammary epithelial cell cultures, they reveal that PKN1 expression interferes with tight junction sealing whereas dominant-negative PKN enhances the process. Together, these observations implicate PKN1 and Rho signalling in the pathway that keeps tight junctions open during pregnancy. The authors suggest that the downregulation of Rho signalling at birth leads to tight junction sealing.
