RUFFLES INDUCED BY SALMONELLA AND OTHER STIMULI DIRECT MACROPINOCYTOSIS OF BACTERIA

RUFFLES are specialized plasma membrane ultrastructures of mammalian cells thought to be integral to growth, development and locomotion1-4. Induced by growth factors5-8, mitogens9 or oncogene expression10,11, ruffles are sites of filamentous actin rearrangement7,8 and are temporally associated with enhanced pinocytosis10,12. But the function of ruffles, their mechanism of induction and their role in pinocytosis are not understood. We have observed formation of structures resembling ruffles associated with the site of entry of invasive Salmonella typhimurium13. Here we report that ruffles elicited by invasive Salmonella directly mediate internalization of non-invasive bacteria in a macropinocytotic fashion, a phenomenon we term 'passive entry'. Furthermore, ruffles induced in the absence of Salmonella also facilitate passive entry. We present evidence that ruffles, common to many signalling events, comprise the macropinocytotic machinery mediating pinocytosis and are subverted by Salmonella so as to enter mammalian cells.