WASP family proteins, more than Arp2/3 activators

Tyler, Joe; Allwood, Ellen G.; Ayscough, Kathryn R.

doi:10.1042/bst20160176

Cited by 31 publications

(24 citation statements)

References 46 publications

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“…The Bzz1-interacting protein Vrp1, however, was involved in the checkpoint. Although both Bzz1 and Vrp1 interact with Las17 (Soulard et al, 2002), a factor that promotes the nucleation of actin by activating the Arp2/3 protein complex (Lechler et al, 2000;Tyler et al, 2016), it is not clear whether Arp2/3 and actin organization are required for the checkpoint. However, given that Bzz1 has many interacting partners, presumably through its SH3 domain (Soulard et al, 2002), it is possible that Bzz1 is involved in the scaffolding or localization of active Hog1 in the checkpoint.…”

Section: Discussionmentioning

confidence: 99%

Genetic dissection of the signaling pathway required for the cell wall integrity checkpoint

Sukegawa

Negishi

Kikuchi

et al. 2018

Journal of Cell Science

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The cell wall integrity checkpoint monitors synthesis of cell wall materials during the cell cycle. Upon perturbation of cell wall synthesis, the cell wall integrity checkpoint is activated, downregulating Clb2 transcription. Here, we identified genes involved in this checkpoint by genetic screening of deletion mutants. In addition to the previously identified dynactin complex, the Las17 complex, in particular the Bzz1 and Vrp1 components, plays a role in this checkpoint. We also revealed that the high osmolarity glycerol (HOG) and cell wall integrity mitogen-activated protein kinase (MAPK) signaling pathways are essential for checkpoint function. The defective checkpoint caused by the deficient dynactin and Las17 complexes was rescued by hyperactivation of the cell wall integrity MAPK pathway, but not by the activated form of Hog1, suggesting an order to these signaling pathways. Mutation of Fkh2, a transcription factor important for Clb2 expression, suppressed the checkpoint-defective phenotype of Las17, HOG MAPK and cell wall integrity MAPK mutations. These results provide genetic evidence that signaling from the cell surface regulates the downstream transcriptional machinery to activate the cell wall integrity checkpoint.

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Section: Discussionmentioning

confidence: 99%

Genetic dissection of the signaling pathway required for the cell wall integrity checkpoint

Sukegawa

Negishi

Kikuchi

et al. 2018

Journal of Cell Science

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“…The formation of plasma membrane protrusions is a complex molecular process, and depends on signals and mechanisms that involve the cytoskeleton and cytoskeleton-associated factors, as well as integral and peripheral membrane proteins (for reviews, see Bisi et al, 2013;Krause and Gautreau, 2014;Alblazi and Siar, 2015;Mooren et al, 2015;Grikscheit and Grosse, 2016;Tyler et al, 2016;Pizarro-Cerda et al, 2017;Schnoor et al, 2017b;Innocenti, 2018). Actin filament branching is a key process in protrusion formation and requires the actin-related protein complex Arp2/3, which needs to be activated by members of the WAVE/ WASP protein family (Pollard et al, 2000;Ti et al, 2011;Welch and Way, 2013;Pollard, 2016;Steffen et al, 2017).…”

Section: Molecular Control Of Jailmentioning

confidence: 99%

Putting VE-cadherin into JAIL for junction remodeling

Cao

Schnittler

2019

Journal of Cell Science

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Junction dynamics of endothelial cells are based on the integration of signal transduction, cytoskeletal remodeling and contraction, which are necessary for the formation and maintenance of monolayer integrity, but also enable repair and regeneration. The VE-cadherincatenin complex forms the molecular basis of the adherence junctions and cooperates closely with actin filaments. Several groups have recently described small actin-driven protrusions at the cell junctions that are controlled by the Arp2/3 complex, contributing to cell junction regulation. We identified these protrusions as the driving force for VE-cadherin dynamics, as they directly induce new VE-cadherin-mediated adhesion sites, and have accordingly referred to these structures as junction-associated intermittent lamellipodia (JAIL). JAIL extend over only a few microns and thus provide the basis for a subcellular regulation of adhesion. The local (subcellular) VE-cadherin concentration and JAIL formation are directly interdependent, which enables autoregulation. Therefore, this mechanism can contribute a subcellularly regulated adaptation of cell contact dynamics, and is therefore of great importance for monolayer integrity and relative cell migration during wound healing and angiogenesis, as well as for inflammatory responses. In this Review, we discuss the mechanisms and functions underlying these actin-driven protrusions and consider their contribution to the dynamic regulation of endothelial cell junctions.

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“…WASP regulates actin polymerization by activating the Arp2/3 complex, allowing nucleation of new actin filaments and cross-linking them from end to side-branch (1). The Arp2/3 complex consists of seven subunits: Arp2, Arp3, Arc-p16, Arc-p20, Arc-p21, Arc-p34 and Arc-p41 (2). Among these subunits, Arc-p41, also known as ARPC1B, is proposed to have a regulatory role, facilitating assembly and maintenance of the whole complex.…”

Section: Introductionmentioning

confidence: 99%

Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in ARPC1B

Somech

Lev

Lee

et al. 2017

The Journal of Immunology

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Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott Aldrich Syndrome Protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multi-subunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency. Here, we describe two brothers with hematopoietic and immunologic symptoms reminiscent of Wiskott Aldrich Syndrome (WAS). However, these patients lacked mutations in any of the genes previously associated with WAS. Whole exome sequencing (WES) revealed a homozygous 2 bp deletion, n.c.G623DEL-TC (p.V208fs), in Arp2/3 complex component ARPC1B, that causes a frame shift resulting in premature termination. Modeling of the disease in zebrafish revealed that ARPC1B plays a critical role in supporting T cell and thrombocyte development. Moreover, the defects in development caused by ARPC1B loss could be rescued by the intact human ARPC1B ortholog, but not by the p.V208fs variant identified in the patient. Moreover, we found that the expression of ARPC1B is restricted to hematopoietic cells, potentially explaining why a mutation in ARPC1B has now been observed as a cause of WAS, while mutations in other, more widely expressed, components of the Arp2/3 complex have not been observed.

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WASP family proteins, more than Arp2/3 activators

Cited by 31 publications

References 46 publications

Genetic dissection of the signaling pathway required for the cell wall integrity checkpoint

Genetic dissection of the signaling pathway required for the cell wall integrity checkpoint

Putting VE-cadherin into JAIL for junction remodeling

Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in ARPC1B

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