A WAVE2–Arp2/3 actin nucleator apparatus supports junctional tension at the epithelial zonula adherens

Verma, Suzie; Han, Siew Ping; Michael, Magdalene; Gómez, Guillermo A.; Yang, Zhe; Teasdale, Rohan D.; Ratheesh, Aparna; Kovács, Éva; Ali, Radiya G.; Yap, Alpha S.

doi:10.1091/mbc.e12-08-0574

Cited by 136 publications

(175 citation statements)

References 43 publications

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“…Quantitative RT-PCR -RT-PCR assay was performed using TaqMAN assay as described previously (27,34). In brief, total RNA was extracted from HeLa control and SNX27 KO cells using QIAshredder and RNeasy Mini Kit from Qiagen (Chadstone, VIC, Australia), and cDNA was synthesized using a SuperScript III First Strand Synthesis System (Thermo Fisher Scientific) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2

Yang

Follett

Kerr

et al. 2018

Journal of Biological Chemistry

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The Alanine, Serine, Cysteine-preferring Transporter 2 (ASCT2; SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian Target of Rapamycin (mTOR) activation. Furthermore, ASCT2 expression has reported in several human cancers making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of Sorting Nexin 27 (SNX27). Using both membrane fractionation and subcellular localisation approaches we demonstrate that the majority of ASCT2 resides at the plasma membrane. This is significantly reduced within CrispR-mediated SNX27 Knock-Out (KO) cell lines, as it is missorted into the lysosomal degradation pathway. The reduction of ASCT2 levels in SNX27 KO cells leads to a decreased glutamine uptake, which in turn inhibits cellular proliferation. SNX27 KO cells also present impaired activation of mTOR complex 1 (mTORC1) pathway and enhanced autophagy. Taken together, our data reveals a role for SNX27 in glutamine uptake and amino acidstimulated mTORC1 activation via the modulation of ASCT2 intracellular trafficking.

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Section: Methodsmentioning

confidence: 99%

Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2

Yang

Follett

Kerr

et al. 2018

Journal of Biological Chemistry

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“…Both N-WASP and WAVE2 was indicated to control adherens junctions in epithelium and endothelium by triggering ARP2/3-mediated actin nucleation and mediate tension development and stabilization. 95,96 However, N-WASP has been indicated to be critical in junction dynamics of both epithelium and endothelium, 11,21,96,97 and thus, is briefly discussed here in more detail. N-WASP consists of an N-terminal WASP-homology domain (WH-domain), a central GTPase-binding domain (GBD), and a conserved carboxyterminal veroprolin central acidic domain (VCA-domain).…”

Section: The Arp2/3 Complex a Central Player In Junction Dynamics Ofmentioning

confidence: 99%

Dynamics between actin and the VE-cadherin/catenin complex

Taha

Schnittler

2014

Cell Adhesion & Migration

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“…3B, graph (Fritzsche and Charras, 2015). FRAP has been used to characterise protein movement (de Beco et al, 2009;Goehring et al, 2010;Renz and Langowski, 2008), protein-protein interaction (Dunham et al, 2004), nuclear export (Wagner et al, 2004), signal transduction (Khait et al, 2016), focal adhesion turn-over (Kumar et al, 2016), cell-cell junction dynamics (Verma et al, 2012;Yamada et al, 2005) or gap junction function via 'gap-FRAP' (Abbaci et al, 2007;Farnsworth et al, 2014). Fluorescence loss in photobleaching (FLIP) Loss of fluorescence in regions adjacent to the bleached region is recorded (Fig.…”

Section: Box 1 Subcellular Imaging Techniquesmentioning

confidence: 99%

Molecular mobility and activity in an intravital imaging setting – implications for cancer progression and targeting

Nobis

Warren

Lucas

et al. 2018

Journal of Cell Science

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Molecular mobility, localisation and spatiotemporal activity are at the core of cell biological processes and deregulation of these dynamic events can underpin disease development and progression. Recent advances in intravital imaging techniques in mice are providing new avenues to study real-time molecular behaviour in intact tissues within a live organism and to gain exciting insights into the intricate regulation of live cell biology at the microscale level. The monitoring of fluorescently labelled proteins and agents can be combined with autofluorescent properties of the microenvironment to provide a comprehensive snapshot of in vivo cell biology. In this Review, we summarise recent intravital microscopy approaches in mice, in processes ranging from normal development and homeostasis to disease progression and treatment in cancer, where we emphasise the utility of intravital imaging to observe dynamic and transient events in vivo. We also highlight the recent integration of advanced subcellular imaging techniques into the intravital imaging pipeline, which can provide in-depth biological information beyond the singlecell level. We conclude with an outlook of ongoing developments in intravital microscopy towards imaging in humans, as well as provide an overview of the challenges the intravital imaging community currently faces and outline potential ways for overcoming these hurdles.

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A WAVE2–Arp2/3 actin nucleator apparatus supports junctional tension at the epithelial zonula adherens

Abstract: WAVE2–Arp2/3 is a major nucleator of actin assembly at the zonula adherens and likely acts in response to junctional Rac signaling. It supports myosin II recruitment to, and tension generation at, the junction.

Cited by 136 publications

References 43 publications

Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2

Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2

Dynamics between actin and the VE-cadherin/catenin complex

Molecular mobility and activity in an intravital imaging setting – implications for cancer progression and targeting

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