The cytolinker Pigs is a direct target and a negative regulator of Notch signalling

Pines, Mary; Housden, Benjamin E.; Bernard, Fred; Bray, Sarah; Röper, Katja

doi:10.1242/dev.043224

Cited by 26 publications

(39 citation statements)

References 45 publications

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“…We had previously observed that full-length Pigs colocalised with both MTs along their length and with some actin structures when it was expressed in the ovary in vivo (Pines et al, 2010). Here, we confirmed that at elevated expression levels in the germline of the ovary, in addition to plus-end tracking, GFPPigsFL also colocalised with both the actin-rich ring canals that connect nurse cells (Fig.…”

Section: Pigs Can Bind Mts and Actin Filaments In Cultured Cells And supporting

confidence: 84%

“…Shot has many well-identified roles from embryogenesis into adulthood, as well as during oocyte specification (Gregory and Brown, 1998;Lee et al, 2000;Röper et al, 2002;Röper and Brown, 2003). pigs 1 mutants are viable but infertile (Pines et al, 2010). Both Shot and Pigs show a ubiquitous expression pattern, although Pigs appears to be expressed only at low levels in many tissues (Fig.…”

Section: Discussionmentioning

confidence: 96%

“…S1). With Shot appearing to be the dominant developmental cytolinker of the CH-Gas2 class in flies, Pigs might add extra functionality under certain conditions, possibly regulated by its responsiveness to Notch (Pines et al, 2010), with loss of Pigs phenotypes masked by a partial redundancy with Shot in many instances.…”

Section: Discussionmentioning

confidence: 99%

“…GFP-PigsFL was the same as previously described (Pines et al, 2010). GFP-PigsCH, GFP-PigsG2 and GFP-PigsG2CT Pigs constructs were cloned into the pUASp-GFP vector (Röper and Brown, 2003).…”

Section: Cloning Of the Gfp-pigs Constructsmentioning

confidence: 99%

“…Proposed functions for the different Gas2-like family members have only recently emerged and include a role for Gas2l3 in the cell cycle as a target of the DREAM complex (Wolter et al, 2012) and a potential role in cell abscission after division (Pe'er et al, 2013). Drosophila has only one Gas2-like family member called Pigs, with a proposed function as a cytolinker whose activity is regulated by Notch signalling (Pines et al, 2010). With single CH domains being able to confer a wealth of interactions, not only to actin but possibly even to MTs, and with Gas2 domains being able to mediate MT binding, but only in the context of surrounding sequences, we wanted to dissect the function of Pigs further and determine in which ways it could interact and influence the cytoskeleton.…”

Section: Introductionmentioning

confidence: 99%

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The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation

Girdler¹,

Applewhite²,

Perry³

et al. 2016

Development

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Coordination between different cytoskeletal systems is crucial for many cell biological functions, including cell migration and mitosis, and also plays an important role during tissue morphogenesis. Proteins of the class of cytoskeletal crosslinkers, or cytolinkers, have the ability to interact with more than one cytoskeletal system at a time and are prime candidates to mediate any coordination. One such class comprises the Gas2-like proteins, combining a conserved calponin-homology-type actin-binding domain and a Gas2 domain predicted to bind microtubules (MTs). This domain combination is also found in spectraplakins, huge cytolinkers that play important roles in many tissues in both invertebrates and vertebrates. Here, we dissect the ability of the single Drosophila Gas2-like protein Pigs to interact with both actin and MT cytoskeletons, both in vitro and in vivo, and illustrate complex regulatory interactions that determine the localisation of Pigs to and its effects on the cytoskeleton.

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Section: Pigs Can Bind Mts and Actin Filaments In Cultured Cells And supporting

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Cloning Of the Gfp-pigs Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation

Girdler¹,

Applewhite²,

Perry³

et al. 2016

Development

Self Cite

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Growth arrest‐specific protein 2 (GAS2) interacts with CXCR4 to promote T‐cell leukemogenesis partially via c‐MYC

Wan

Zhang

et al. 2022

Molecular Oncology

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Although growth arrest‐specific protein 2 (GAS2) promotes the growth of T‐cell acute lymphoblastic leukemia (T‐ALL) cells in culture, the effect of GAS2 on T‐cell leukemogenesis has not been studied, and the mechanism remains unclear. In the present study, xenograft studies showed that GAS2 silencing impaired T‐cell leukemogenesis and decreased leukemic cell infiltration. Mechanistically, GAS2 regulated the protein expression of C‐X‐C chemokine receptor type 4 (CXCR4) rather than its transcript expression. Immunoprecipitation revealed that GAS2 interacted with CXCR4, and confocal analysis showed that GAS2 was partially co‐expressed with CXCR4, which provided a strong molecular basis for GAS2 to regulate CXCR4 expression. Importantly, CXCR4 overexpression alleviated the inhibitory effect of GAS2 silencing on the growth and migration of T‐ALL cells. Moreover, GAS2 or CXCR4 silencing inhibited the expression of NOTCH1 and c‐MYC. Forced expression of c‐MYC rescued the growth suppression induced by GAS2 or CXCR4 silencing. Meanwhile, GAS2 deficiency, specifically in blood cells, had a mild effect on normal hematopoiesis, including T‐cell development, and GAS2 silencing did not affect the growth of normal human CD3+ or CD34+ cells. Overall, our data indicate that GAS2 promotes T‐cell leukemogenesis through its interaction with CXCR4 to activate NOTCH1/c‐MYC, whereas impaired GAS2 expression has a mild effect on normal hematopoiesis. Therefore, our study suggests that targeting the GAS2/CXCR4 axis is a potential therapeutic strategy for T‐ALL.

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Modulation of cell morphogenesis by tousled‐like kinase in the Drosophila follicle cell

Yeh¹,

Huang²,

Lan³

et al. 2015

Developmental Dynamics

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Background: Tousled-like kinase (Tlk) is a conserved serine/threonine kinase regulating DNA replication, chromatin assembly, and DNA repair. Previous studies have suggested that Tlk is involved in cell morphogenesis in vitro. In addition, tlk genetically interact with Rho1, which encodes a key regulator of the cytoskeleton. However, whether Tlk plays a physiological role in cell morphogenesis and cytoskeleton rearrangement remains unknown. Results: In tlk mutant follicle cells, area of the apical domain was reduced. The density of microtubules was increased in tlk mutant cells. The density of actin filaments was increased in the apical region and decreased in the basal region. Because area of the apical domain was reduced, we examined the levels of proteins located in the apical region by using immunofluorescence. The fluorescence intensities of two adherens junction proteins Armadillo (Arm) and DE-cadherin (DE-cad), atypical protein kinase C (aPKC), and Notch, were all increased in tlk mutant cells. The basolateral localized Discs large (Dlg) shifted apically in tlk mutant cells. Conclusions: Increase of protein densities in the apical region might be resulted from disruption of the cytoskeleton and shrinkage of the apical domain. Together, these data suggest a novel role of Tlk in maintaining cell morphology, possibly through modulating the cytoskeleton. Developmental Dynamics 244:852-865, 2015. V C 2015 Wiley Periodicals, Inc.

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The cytolinker Pigs is a direct target and a negative regulator of Notch signalling

Cited by 26 publications

References 45 publications

The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation

The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation

Growth arrest‐specific protein 2 (GAS2) interacts with CXCR4 to promote T‐cell leukemogenesis partially via c‐MYC

Modulation of cell morphogenesis by tousled‐like kinase in the Drosophila follicle cell

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