Hierarchical Regulation of WASP/WAVE Proteins

Padrick, Shae B.; Cheng, Hui Chun; Ismail, Ahmed Rageh; Panchal, Sanjay C.; Doolittle, Lynda K.; Kim, Soyeon; Skehan, Brian; Umetani, Junko; Brautigam, Chad A.; Leong, John M.; Rosen, Michael K.

doi:10.1016/j.molcel.2008.10.012

Cited by 197 publications

(268 citation statements)

References 55 publications

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“…More generally, our observations have provided a quantitative understanding of Arp2/3-mediated actin network assembly dynamics, and revealed an inherent baseline inefficiency and complexity to the branch formation mechanism. There are multiple points in this mechanism at which the efficiency of daughter filament nucleation could be increased by factors that stimulate Arp2/3 complex, including VCA and non-VCA domains in WASp, factors that multimerize WASp, cortactin, and coronin (20,21,(38)(39)(40). Further, their combined effects may allow the integration of multiple stimulatory pathways.…”

Section: Discussionmentioning

confidence: 99%

Pathway of actin filament branch formation by Arp2/3 complex revealed by single-molecule imaging

Smith

Daugherty-Clarke

Goode

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

101

137

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Actin filament nucleation by actin-related protein (Arp) 2/3 complex is a critical process in cell motility and endocytosis, yet key aspects of its mechanism are unknown due to a lack of real-time observations of Arp2/3 complex through the nucleation process. Triggered by the verprolin homology, central, and acidic (VCA) region of proteins in the Wiskott-Aldrich syndrome protein (WASp) family, Arp2/3 complex produces new (daughter) filaments as branches from the sides of preexisting (mother) filaments. We visualized individual fluorescently labeled Arp2/3 complexes dynamically interacting with and producing branches on growing actin filaments in vitro. Branch formation was strikingly inefficient, even in the presence of VCA: only ∼1% of filament-bound Arp2/3 complexes yielded a daughter filament. VCA acted at multiple steps, increasing both the association rate of Arp2/3 complexes with mother filament and the fraction of filament-bound complexes that nucleated a daughter. The results lead to a quantitative kinetic mechanism for branched actin assembly, revealing the steps that can be stimulated by additional cellular factors.

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Section: Discussionmentioning

confidence: 99%

Pathway of actin filament branch formation by Arp2/3 complex revealed by single-molecule imaging

Smith

Daugherty-Clarke

Goode

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

101

137

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“…Finally, oligomerization of WASP and WAVE proteins has been shown to synergistically increase Arp2/3-dependent F-actin nucleation (Padrick et al, 2008). This is accomplished by two WCA domains interacting with two unique sites on the Arp2/3 complex simultaneously to promote actin nucleation (Padrick et al, 2011). binding WASH homology domain 2 (WHD2), a proline-rich region and C-terminal WCA domain.…”

Section: Jmymentioning

confidence: 99%

Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

181

172

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Proteins of the Wiskott–Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network. Recent studies have also identified roles for WASP family members in promoting actin dynamics at the centrosome, influencing nuclear shape and membrane remodeling events leading to the generation of autophagosomes. Interestingly, several WASP family members have also been observed in the nucleus where they directly influence gene expression by serving as molecular platforms for the assembly of epigenetic and transcriptional machinery. In this Cell Science at a Glance article and accompanying poster, we provide an update on the subcellular roles of WHAMM, JMY and WASH (also known as WASHC1), as well as their mechanisms of regulation and emerging functions within the cell.

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“…WASP exists in an autoinhibited conformation (Miki et al 1998). The mechanism of WASPfamily protein regulation involves overcoming an autoinhibitory intramolecular interaction and subsequent oligomerization to drive Arp2/ 3-dependent actin assembly (Padrick et al 2008). N-WASP is allosterically activated and oligomerized by binding to PtdIns(4,5)P 2 and GTP-Cdc42 (Prehoda et al 2000;Rohatgi et al 2000).…”

Section: Branched Actin Networkmentioning

confidence: 99%

Phosphoinositides in Cell Architecture

Shewan

Eastburn²,

Mostov

2011

Cold Spring Harbor Perspectives in Biology

173

159

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Inositol phospholipids have been implicated in almost all aspects of cellular physiology including spatiotemporal regulation of cellular signaling, acquisition of cellular polarity, specification of membrane identity, cytoskeletal dynamics, and regulation of cellular adhesion, motility, and cytokinesis. In this review, we examine the critical role phosphoinositides play in these processes to execute the establishment and maintenance of cellular architecture. Epithelial tissues perform essential barrier and transport functions in almost all major organs. Key to their development and function is the establishment of epithelial cell polarity. We place a special emphasis on highlighting recent studies demonstrating phosphoinositide regulation of epithelial cell polarity and how individual cells use phosphoinositides to further organize into epithelial tissues.P hosphoinositides (PIs) are essential components of cellular membranes in eukaryotes. Though these specialized lipids comprise less than 1% of the cellular lipid cohort, they play key roles in many fundamental biological processes (Di Paolo and De Camilli 2006;Saarikangas et al. 2010). PIs possess such far ranging roles by serving as specialized membrane docking sites for effectors of numerous cellular signal transduction cascades. PIs also serve as precursors of lipid second messengers. They are concentrated on the cytosolic face of cellular membranes (Fig. 1A) and rapidly diffuse within the plane of the membrane. Reversible phosphorylation of the myo-inositol head group of phosphatidylinositol (PtdIns) at positions 3, 4, and 5 (Fig. 1B) gives rise to the seven PI isoforms identified in eukaryotic cells. PtdIns(4)P and PtdIns(4,5)P 2 are constitutively present in membranes and comprise the largest pool of cellular PIs, whereas PtdIns(3,4,5)P 3 is essentially undetectable in most types of unstimulated cells (Lemmon and Ferguson 2000;Saarikangas et al. 2010).The spatiotemporally regulated production and turnover of phosphoinositides is crucial for localized PI signaling and function. Numerous phosphatidylinositol kinases and phosphatases are involved in regulating the metabolism of the various PI isoforms (Fig. 1)

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Hierarchical Regulation of WASP/WAVE Proteins

Cited by 197 publications

References 55 publications

Pathway of actin filament branch formation by Arp2/3 complex revealed by single-molecule imaging

Pathway of actin filament branch formation by Arp2/3 complex revealed by single-molecule imaging

Cellular functions of WASP family proteins at a glance

Phosphoinositides in Cell Architecture

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