title: Polarity proteins and Rho GTPases cooperate to spatially organise epithelial actin-based protrusions.
abstract: Different actin-filament-based structures co-exist in many cells. Here, we characterise dynamic actin-based protrusions that form at distinct positions within columnar epithelial cells, focusing on basal filopodia and sheet-like intermediate-level protrusions that extend between surrounding epithelial cells. Using a genetic analysis, we found that the form and distribution of these actin-filament-based structures depends on the activities of apical polarity determinants, not on basal integrin signalling. Bazooka/Par3 acts upstream of the RacGEF Sif/TIAM1 to limit filopodia to the basal domain, whereas Cdc42, aPKC and Par6 are required for normal protrusion morphology and dynamics. Downstream of these polarity regulators, Sif/TIAM1, Rac, SCAR and Arp2/3 complexes catalyse actin nucleation to generate lamellipodia and filopodia, whose form depends on the level of Rac activation. Taken together, these data reveal a role for Baz/Par3 in the establishment of an intercellular gradient of Rac inhibition, from apical to basal, and an intimate association between different apically concentrated Par proteins and Rho-family GTPases in the regulation of the distribution and structure of the polarised epithelial actin cytoskeleton.
authors.affiliation: MRC-Laboratory of Molecular Cell Biology, UCL, London, WC1E 6BT, UK. marios.georgiou@ucl.ac.uk
authors.forename: Marios
authors.initials: M
authors.lastname: Georgiou
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D016764:Cell Polarity; D022081:Cell Surface Extensions / Q000473:pathology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004330:Drosophila; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D050505:Mutant Proteins; C509689:PARD3 protein, human; D020741:rho GTP-Binding Proteins