PMID- 8223707 OWN - NLM STAT- MEDLINE DCOM- 19931206 LR - 20091119 IS - 0171-9335 (Print) IS - 0171-9335 (Linking) VI - 61 IP - 1 DP - 1993 Jun TI - Circular ruffle formation and closure lead to macropinocytosis in hepatocyte growth factor/scatter factor-treated cells. PG - 44-53 AB - Treatment with hepatocyte growth factor/scatter factor (HGF/SF) rapidly induced the formation of conspicuous circular ruffles on the apical surfaces of two kidney cell lines, MDCK and PtK2. The ruffles were found to contain significant amounts of F-actin and myosin as judged by immunofluorescence microscopy. Time-lapse photomicroscopy demonstrated that the ruffles constrict, closing over, and were followed by the formation of phase bright structures. That these structures were macropinocytotic vesicles was confirmed using fluorescein isothiocyanate (FITC)-dextran as a marker for fluid uptake. It is hypothesized that the constriction of the ruffles followed by membrane fusion causes the vesicles to form. Treatment with suramin blocked both circular ruffle formation and scattering, suggesting that ligand binding was the causal agent for ruffle formation. The drugs amiloride and SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid) also completely inhibited ruffle formation, suggesting that ion transport was an early consequence of HGF/SF binding and that these transport effects had a major role in the cytoskeletal changes leading to circular ruffle formation. The appearance of macropinocytotic vesicles was also blocked by amiloride treatment. Surprisingly though, subsequent scattering was not blocked by amiloride treatment, although suramin and SITS both entirely inhibited scattering. FAU - Dowrick, P AU - Dowrick P AD - School of Biological Sciences, University of East Anglia, Norwich/United Kingdom. FAU - Kenworthy, P AU - Kenworthy P FAU - McCann, B AU - McCann B FAU - Warn, R AU - Warn R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Cell Biol JT - European journal of cell biology JID - 7906240 RN - 0 (Actins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 3.6.4.1 (Myosins) SB - IM MH - 3T3 Cells MH - Actins/drug effects MH - Animals MH - Cell Line MH - Dogs MH - Hepatocyte Growth Factor/*pharmacology MH - Kidney/*drug effects/ultrastructure MH - Mice MH - Microscopy, Electron, Scanning MH - Microscopy, Phase-Contrast MH - Myosins/drug effects MH - Pinocytosis/*drug effects EDAT- 1993/06/01 00:00 MHDA- 1993/06/01 00:01 CRDT- 1993/06/01 00:00 PHST- 1993/06/01 00:00 [pubmed] PHST- 1993/06/01 00:01 [medline] PHST- 1993/06/01 00:00 [entrez] PST - ppublish SO - Eur J Cell Biol. 1993 Jun;61(1):44-53.