Alternatively, this link to the actin cytoskeleton can occur through scaffolding proteins that contain specific phospholipid-binding motifs, such as pleckstrin homology (PH) domains found in proteins such as phospholipase C (PLC), dynamin ( Flesch et al., 2005 Harlan et al., 1994 Vallis et al., 1999), or Bin/amphiphysin/Rvs (BAR)-domain-containing proteins (reviewed by Itoh and De Camilli, 2006 Tsujita et al., 2006). The actin cytoskeleton can be linked to the plasma membrane through a diverse array of actin-binding proteins that interact directly with phosphoinositides, frequently phosphatidylinositol 4,5-bisphosphate, present in the inner leaflet of the plasma membrane, such as the Wiscott–Aldrich syndrome protein (WASP) family proteins ( Miki et al., 1996 Oikawa et al., 2004), actin depolymerizing factor (ADF)/cofilins ( Zhao et al., 2010) and the small Rho-like GTPases ( Yoshida et al., 2009). The coordination of plasma membrane deformation and actin polymerization is critical for cellular processes including chemotaxis, endocytosis, polarity and cytokinesis ( Ford et al., 2002 Frost et al., 2007 Han et al., 2006 Janetopoulos et al., 2005 Martin-Belmonte et al., 2007 Vallis et al., 1999). The plasma membrane and actin cytoskeleton work in concert to create, maintain, and modify cell shape ( Raucher et al., 2000 Sheetz and Dai, 1996). Overall, our results provide novel insights into the functional diversity of the membrane deformation properties of this subclass of F-BAR-domains required for cell morphogenesis. Interestingly, acute phosphatidylinositol 4,5-bisphosphate depletion in cells does not interfere with plasma membrane localization of F-BAR(2), which is compatible with our result showing that F-BAR(2) binds to a broad range of negatively-charged phospholipids present at the plasma membrane, including phosphatidylserine (PtdSer). We also show that the molecular dynamic properties of F-BAR(2) at the membrane are partially dependent on F-Actin. As measured by fluorescence recovery after photobleaching, F-BAR(2) displays faster molecular dynamics than F-BAR(3) and F-BAR(1) at the plasma membrane, which correlates well with its increased potency to induce filopodia. These three F-BAR domains can heterodimerize, and they act synergistically towards filopodia induction in COS7 cells. F-BAR(3) induces filopodia in both cell types, though less potently than F-BAR(2), whereas F-BAR(1) prevents filopodia formation in cortical neurons and reduces plasma membrane dynamics. Here, we demonstrate that the F-BAR domains of two closely related family members, srGAP1 and srGAP3 display significantly different membrane deformation properties in non-neuronal COS7 cells and in cortical neurons. We have recently shown that Slit-Robo GTPase-activating protein 2 (srGAP2) regulates neuronal morphogenesis through the ability of its F-BAR domain to regulate membrane deformation and induce filopodia formation. ![]() Coordination of membrane deformation and cytoskeletal dynamics lies at the heart of many biological processes critical for cell polarity, motility and morphogenesis.
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