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Sci. STKE, 30 January 2007
Vol. 2007, Issue 371, p. tw37
[DOI: 10.1126/stke.3712007tw37]

EDITORS' CHOICE

Cell Biology A New Way to Make Filopodia?

Nancy R. Gough

Science's STKE, AAAS, Washington, DC 20005, USA

Filopodia are slender actin-rich protrusions that are most often associated with activation of the guanosine triphosphatase (GTPase) Cdc42 and the actin regulatory proteins, the ARP2/3 complex, Wiskott-Aldrich syndrome protein (WASP), and proteins of the Ena/VASP family. An alternate mechanism involving the GTPase Rif and the mDia2 protein, instead of Cdc42 and ARP2/3, has also been reported. Sigal et al. provide evidence for yet another mechanism by which filopodia may be formed. When they overexpressed lipid-phosphatase-related protein 1 (LPR1) in Cos7 or HeLa cells, they noted an increase in the formation of filopodia along the cell periphery and dorsal surface. However, LPR1-induced filopodia formed even when dominant-negative Cdc42, or peptide inhibitors of Cdc42 or ARP2/3, or dominant-negative Rif were coexpressed with LPR1 in the cells. Colocalization studies suggested that the actin structures in the LPR1-induced filopodia had a unique composition and did not include components of focal adhesion complexes characteristic of Cdc42-stimulated filopodia or VASP or two VASP homologs. The actin-bundling protein fascin was present along the shafts of the LPR1-induced filopodia, and myosin X was found in the tips of the filopodia. In MVD7 cells, which are engineered to lack all three members of the VASP family, LPR1 stimulated filopodia formation. RNAi experiments in a human ovary surface epithelial cell line, SK-OV-3, which is an invasive and motile cell line, showed that there was a substantial decrease in the formation of filopodia when LPR1 abundance was decreased. LPR1 is predicted to have six transmembrane domains, but the putative catalytic region lacks certain conserved residues that are required for activity in other members of the lipid phosphatase and phosphotransferase (LPT) family. When expressed in Sf9 cells, which natively have low lipid phosphatase and phosphotransferase activity, detergent extracts of the LPR1-expressing cells showed no phosphatase activity against any of the four common substrates of the LPT family. However, mutation of residues in the pseudocatalytic region disrupted the filopodia-stimulating activity of LPR1; thus, lipid interactions may still be important for the function of LPR1.

Y. J. Sigal, O. A. Quintero, R. E. Cheney, A. J. Morris, Cdc42 and ARP2/3-independent regulation of filopodia by an integral membrane lipid-phosphatase-related protein. J. Cell Sci. 120, 340-352 (2007). [Abstract] [Full Text]

Citation: N. R. Gough, A New Way to Make Filopodia? Sci. STKE 2007, tw37 (2007).


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