FASCIN, AN ACTIN-BUNDLING PROTEIN, INDUCES MEMBRANE PROTRUSIONS AND INCREASES CELL MOTILITY OF EPITHELIAL-CELLS

Fascin is an actin-bundling protein that is found in membrane ruffles, microspikes, and stress fibers. The expression of fascin is greatly i ncreased in many transformed cells, as well as in specialized normal c ells including neuronal cells and antigen-presenting dendritic cells. A morphological characteristic common to these cells expressing high l evels of fascin is the development of many membrane protrusions in whi ch fascin is predominantly present. To examine whether fascin contribu tes to the alterations in microfilament organization at the cell perip hery, we have expressed fascin in LLC-PK1 epithelial cells to levels a s high as those found in transformed cells and in specialized normal c ells. Expression of fascin results in large changes in morphology, the actin cytoskeleton, and cell motility: fascin-transfected cells form an increased number of longer and thicker microvilli on apical surface s, extend lamellipodia-like structures at basolateral surfaces, and sh ow disorganization of cell-cell contacts. Cell migration activity is i ncreased by 8-17 times when assayed by modified Boyden chamber. Microi njection of a fascin protein into LLC-PK1 cells causes similar morphol ogical alterations including the induction of lamellipodia at basolate ral surfaces and formation of an increased number of microvilli on api cal surfaces. Furthermore, microinjection of fascin into REF-52 cells, normal fibroblasts, induces the formation of many lamellipodia at all regions of cell periphery. These results together suggest that fascin is directly responsible for membrane protrusions through reorganizati on of the microfilament cytoskeleton at the cell periphery.