Monensin inhibits initial spreading of cultured human fibroblasts

Abstract

The monovalent ionophore, monensin, inhibits the secretion of both pro-collagen and fibronectin in cultured human fibroblasts1–3 and other cell types4–7. The block to secretion is due to the ability of monensin to suppress the export of these secretory proteins from the Golgi apparatus3,8,9. As such proteins are known to be implicated in the adhesion, spreading and movement of cultured fibroblasts10,11, it might be expected that monensin treatment would interfere with these processes. However, it has recently been reported9 that monensin-treated human embryonal fibroblasts attached and spread onto glass substrata to the same extent as untreated cells, although at later stages they fail to develop focal adhesion sites. However, these experiments were performed using medium supplemented with fetal calf serum (FCS). We now demonstrate that in the absence of FCS, while monensin has little or no effect on the initial adhesion of fibroblasts to the substratum, subsequent spreading is much reduced. The inhibition of spreading is noticeable within 30 min of plating and is maintained for at least 100 min in monensin-free medium following prolonged pre-incubation of the cells with monensin.