Figure 1.
How does the WAVE complex achieve the proper spatial organization for lamellipodial generation? (A) Homologous actin NPFs organize different cell morphologies. Given that the homologous NPFs N-WASP and the WAVE complex are both activated by homologous GTPases, associated with homologous BAR domains, stimulated Arp2/3 complex activation, and stripped off the membrane as a function of this actin polymerization, how do they organize different cellular morphologies? N-WASP canonically associates with filopodia, invadopodia, and endocytosis, whereas the WAVE complex associates with sheet-like lamellipodia. Left: Chick cranial neural crest cell with multiple filopodia from Genuth et al. (2018). Right: Head-on view of a neutrophil-like dHL60 lamellipodium (ChimeraX rendering of a confocal z-stack). Scale bars: 10 µm (left) and 5 µm (right). (B) Schematic of how NPF spatial organization could instruct the resulting actin morphologies. N-WASP’s positive feedback results in the focal organization expected for one-dimensional, finger-like actin structures (Banjade and Rosen, 2014). To build lamellipodia, does the WAVE complex’s positive feedback result in a linear organization to template 2D, sheet-like actin structures? (C) Hem1-EGFP, a fluorescently tagged subunit of the WAVE complex, has a linear organization at tips of lamellipodia in chemoattractant-stimulated (10 nM fMLP) dHL60 cells. Top: 3D imaging of the WAVE complex at tips of extending lamellipodia; left, widefield 3D reconstruction; right, lattice light sheet reconstruction of ruffles from a head-on view. Bottom: WAVE complex’s linear organization viewed from the ventral plasma membrane; simultaneous TIRF imaging of Hem1-EGFP (green) and membrane CellMask DeepRed dye (gray). Scale bars: 5 µm and 2 µm (bottom right). See Video 1.

How does the WAVE complex achieve the proper spatial organization for lamellipodial generation? (A) Homologous actin NPFs organize different cell morphologies. Given that the homologous NPFs N-WASP and the WAVE complex are both activated by homologous GTPases, associated with homologous BAR domains, stimulated Arp2/3 complex activation, and stripped off the membrane as a function of this actin polymerization, how do they organize different cellular morphologies? N-WASP canonically associates with filopodia, invadopodia, and endocytosis, whereas the WAVE complex associates with sheet-like lamellipodia. Left: Chick cranial neural crest cell with multiple filopodia from Genuth et al. (2018). Right: Head-on view of a neutrophil-like dHL60 lamellipodium (ChimeraX rendering of a confocal z-stack). Scale bars: 10 µm (left) and 5 µm (right). (B) Schematic of how NPF spatial organization could instruct the resulting actin morphologies. N-WASP’s positive feedback results in the focal organization expected for one-dimensional, finger-like actin structures (Banjade and Rosen, 2014). To build lamellipodia, does the WAVE complex’s positive feedback result in a linear organization to template 2D, sheet-like actin structures? (C) Hem1-EGFP, a fluorescently tagged subunit of the WAVE complex, has a linear organization at tips of lamellipodia in chemoattractant-stimulated (10 nM fMLP) dHL60 cells. Top: 3D imaging of the WAVE complex at tips of extending lamellipodia; left, widefield 3D reconstruction; right, lattice light sheet reconstruction of ruffles from a head-on view. Bottom: WAVE complex’s linear organization viewed from the ventral plasma membrane; simultaneous TIRF imaging of Hem1-EGFP (green) and membrane CellMask DeepRed dye (gray). Scale bars: 5 µm and 2 µm (bottom right). See Video 1.

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