Dynamics of Core Planar Polarity Protein Turnover and Stable Assembly into Discrete Membrane Subdomains

Strutt, Helen; Warrington, Samantha J.; Strutt, David

doi:10.1016/j.devcel.2011.03.018

Cited by 119 publications

(188 citation statements)

References 40 publications

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“…Alternatively, Vang might affect the formation or stability of Stan<<Stan Fz bridges indirectly, consistent with evidence implicating it in the trafficking of proteins and lipids to the cell surface (Lee et al, 2003). For example, Strutt and Strutt have presented evidence that any Stan or Stan Fz on the cell surface that is not engaged in Stan<<Stan Fz bridges is rapidly endocytosed and recycled to other sites on the cell surface Strutt et al, 2011). Vang activity could bias this process in favour of Stan, thereby enhancing its capacity to form bridges with Stan Fz .…”

Section: Molecular Observations On Bridges and Their Implicationsmentioning

confidence: 69%

Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity

Struhl¹,

Casal

Lawrence

2012

Development

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SUMMARYMany epithelia have a common planar cell polarity (PCP), as exemplified by the consistent orientation of hairs on mammalian skin and insect cuticle. One conserved system of PCP depends on Starry night (Stan, also called Flamingo), an atypical cadherin that forms homodimeric bridges between adjacent cells. Stan acts together with other transmembrane proteins, most notably Frizzled (Fz) and Van Gogh (Vang, also called Strabismus). Here, using an in vivo assay for function, we show that the quintessential core of the Stan system is an asymmetric intercellular bridge between Stan in one cell and Stan acting together with Fz in its neighbour: such bridges are necessary and sufficient to polarise hairs in both cells, even in the absence of Vang. By contrast, Vang cannot polarise cells in the absence of Fz; instead, it appears to help Stan in each cell form effective bridges with Stan plus Fz in its neighbours. Finally, we show that cells containing Stan but lacking both Fz and Vang can be polarised to make hairs that point away from abutting cells that express Fz. We deduce that each cell has a mechanism to estimate and compare the numbers of asymmetric bridges, made between Stan and Stan plus Fz, that link it with its neighbouring cells. We propose that cells normally use this mechanism to read the local slope of tissue-wide gradients of Fz activity, so that all cells come to point in the same direction.

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Section: Molecular Observations On Bridges and Their Implicationsmentioning

confidence: 69%

Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity

Struhl¹,

Casal

Lawrence

2012

Development

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“…Here, we describe the action of useful reporters for in vivo imaging of the dynamic localization of vertebrate core PCP proteins in Xenopus, further supplementing this established rapid and tractable vertebrate PCP model. The observed behavior of symmetrically distributed PCP complexes later resolving into asymmetric accumulations is reminiscent of early PCP patterning events in the fly wing (Seifert and Mlodzik, 2007;Strutt and Strutt, 2009;Strutt et al, 2011). In addition, there appears to be a common theme of increasing asymmetry coinciding with increasing polarized cellular behaviors.…”

Section: Discussionmentioning

confidence: 86%

“…In brief, Pk binds and inhibits the membrane localization of Dsh, but Dgo competes with Pk for Dsh binding, promoting the association of Dsh with Fz (Jenny et al, 2005;Tree et al, 2002). Pk also physically interacts with Vang, and this interaction leads to the clustering of Vang on the opposite side of the cell (Bastock et al, 2003;Jenny et al, 2003;Strutt et al, 2011). In addition, Pk mediates the internalization of Vang or FmiVang molecules that are not associated with stable, patterned complexes (Cho et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Control of vertebrate core PCP protein localization and dynamics by Prickle2

Butler

Wallingford

2015

Development

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Planar cell polarity (PCP) is a ubiquitous property of animal tissues and is essential for morphogenesis and homeostasis. In most cases, this fundamental property is governed by a deeply conserved set of 'core PCP' proteins, which includes the transmembrane proteins Van Gogh-like (Vangl) and Frizzled (Fzd), as well as the cytoplasmic effectors Prickle (Pk) and Dishevelled (Dvl). Asymmetric localization of these proteins is thought to be central to their function, and understanding the dynamics of these proteins is an important challenge in developmental biology. Among the processes that are organized by the core PCP proteins is the directional beating of cilia, such as those in the vertebrate node, airway and brain. Here, we exploit the live imaging capabilities of Xenopus to chart the progressive asymmetric localization of fluorescent reporters of Dvl1, Pk2 and Vangl1 in a planar polarized ciliated epithelium. Using this system, we also characterize the influence of Pk2 on the asymmetric dynamics of Vangl1 at the cell cortex, and we define regions of Pk2 that control its own localization and those impacting Vangl1. Finally, our data reveal a striking uncoupling of Vangl1 and Dvl1 asymmetry. This study advances our understanding of conserved PCP protein functions and also establishes a rapid, tractable platform to facilitate future in vivo studies of vertebrate PCP protein dynamics.

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“…Dsh and Fz become localized to the distal edge of each cell, Pk and Vang to the proximal edge (Strutt and Strutt, 2009). Some degree of polarization is also evident in prepupal stages (Aigouy et al, 2010;Strutt et al, 2011). Cells in the prepupal leg epithelium are mostly irregular in shape and size, unlike the wing, making it difficult to detect clear organization in cell morphology or protein distribution.…”

Section: Asymmetric Distribution Of Core Pcp Proteins In the Developimentioning

confidence: 99%

Planar cell polarity controls directional Notch signaling in theDrosophilaleg

et al. 2012

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SUMMARYThe generation of functional structures during development requires tight spatial regulation of signaling pathways. Thus, in Drosophila legs, in which Notch pathway activity is required to specify joints, only cells distal to ligand-producing cells are capable of responding. Here, we show that the asymmetric distribution of planar cell polarity (PCP) proteins correlates with this spatial restriction of Notch activation. Frizzled and Dishevelled are enriched at distal sides of each cell and hence localize at the interface with ligand-expressing cells in the non-responding cells. Elimination of PCP gene function in cells proximal to ligand-expressing cells is sufficient to alleviate the repression, resulting in ectopic Notch activity and ectopic joint formation. Mutations that compromise a direct interaction between Dishevelled and Notch reduce the efficacy of repression. Likewise, increased Rab5 levels or dominantnegative Deltex can suppress the ectopic joints. Together, these results suggest that PCP coordinates the spatial activity of the Notch pathway by regulating endocytic trafficking of the receptor.

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Dynamics of Core Planar Polarity Protein Turnover and Stable Assembly into Discrete Membrane Subdomains

Cited by 119 publications

References 40 publications

Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity

Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity

Control of vertebrate core PCP protein localization and dynamics by Prickle2

Planar cell polarity controls directional Notch signaling in theDrosophilaleg

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