Wnt Signal Production, Secretion, and Diffusion

Maurice, Madelon M.; Korswagen, Hendrik C.

doi:10.1002/9781118444122.ch1

Cited by 3 publications

(3 citation statements)

References 82 publications

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“…For instance, glypicans enhance cytoneme stability, and Wnt ligands could enter or exit cytonemes in exosomes, presenting points of intersection among these modes of transport (107,108). Other reviews focused on intercellular transport of Wnts offer comprehensive overviews on the subject (109)(110)(111)(112)(113).…”

Section: Wnt Signal Production and Secretionmentioning

confidence: 99%

The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators

Rim

Clevers

Nusse

2022

Annu. Rev. Biochem.

249

130

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The Wnt pathway is central to a host of developmental and disease-related processes. The remarkable conservation of this intercellular signaling cascade throughout metazoan lineages indicates that it coevolved with multicellularity to regulate the generation and spatial arrangement of distinct cell types. By regulating cell fate specification, mitotic activity, and cell polarity, Wnt signaling orchestrates development and tissue homeostasis, and its dysregulation is implicated in developmental defects, cancer, and degenerative disorders. We review advances in our understanding of this key pathway, from Wnt protein production and secretion to relay of the signal in the cytoplasm of the receiving cell. We discuss the evolutionary history of this pathway as well as endogenous and synthetic modulators of its activity. Finally, we highlight remaining gaps in our knowledge of Wnt signal transduction and avenues for future research. Expected final online publication date for the Annual Review of Biochemistry, Volume 91 is June 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Wnt Signal Production and Secretionmentioning

confidence: 99%

The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators

Rim

Clevers

Nusse

2022

Annu. Rev. Biochem.

249

130

View full text Add to dashboard Cite

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“…Wls functions downstream of Porcn, is also highly conserved in evolution (Banziger et al, 2006;Bartscherer et al, 2006) and loss of function assays unveiled specificity for transport of Wnt ligands to the plasma membrane (Banziger et al, 2006). Like other molecules involved in vesicular trafficking, Wls is recycled (Maurice and Korswagen, 2014). In mouse, but not in Drosophila, Wls was found to be a direct target of the Wnt/b-catenin pathway suggesting that Wnt proteins can stimulate their own secretion by upregulating Wls expression (Fu et al, 2009;Herr and Basler, 2012).…”

Section: Wnt Signaling During Heart Developmentmentioning

confidence: 99%

“…A further level of complexity in the regulation of Wnt signaling is found at the level of posttranscriptional modifications and secretion of Wnts (Cheng and Xu, ). An array of proteins has been described to be involved in the transport of Wnts from the endoplasmic reticulum by means of the Golgi to the membrane for secretion as well as in the lipid‐modification and glycosylation of Wnt proteins (for review, see Maurice and Korswagen, ). In this review, we highlight two proteins, Porcupine (Porcn) and Wntless (Wls), because of their potential role in heart development.…”

Section: Wnt Signaling During Heart Developmentmentioning

confidence: 99%

Wnt signaling in the heart fields: Variations on a common theme

Ruiz‐Villalba

Hoppler

Hoff

2016

Developmental Dynamics

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Wnt signaling plays an essential role in development and differentiation. Heart development is initiated with the induction of precardiac mesoderm requiring the tightly and spatially controlled regulation of canonical and noncanonical Wnt signaling pathways. The role of Wnt signaling in subsequent development of the heart fields is to a large extent unclear. We will discuss the role of Wnt signaling in the development of the arterial and venous pole of the heart, highlighting the dual roles of Wnt signaling with respect to its time-and dosage-dependent effects and the balance between the canonical and noncanonical signaling. Canonical signaling appears to be involved in retaining the cardiac precursors in a proliferative and precursor state, whereas noncanonical signaling promotes their differentiation. Thereafter, both canonical and noncanonical signaling regulate specific steps in differentiation of the cardiac compartments. Because heart development is a contiguous, rather than a sequential, process, analyses tend only to show a single timeframe of development. The repetitive alternating and reciprocal effect of canonical and noncanonical signaling is lost when studied in homogenates. Without the simultaneous in vivo visualization of the different Wnt signaling pathways, the mechanism of Wnt signaling in heart development remains elusive. Developmental Dynamics 245:294-306, 2016. V C 2015 Wiley Periodicals, Inc.

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Cell‐to‐Cell Signalling in Development: Wnt Signalling

Hoppler

Nakamura

2014

Encyclopedia of Life Sciences

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Wnt signalling is an important cell‐to‐cell signalling mechanism, which is generally conserved among multicellular animals. Wnt signalling operates in the embryo and in adult stem cells, but also in human cancers. Frizzled receptors in the cell membrane are critical functional intermediaries between the extracellular Wnt signal and diverse signal transduction mechanisms that can be activated inside different responding cells. Coreceptors are involved in selecting more specific intracellular signal transduction mechanisms. Frizzled receptors and other Wnt signalling molecules are localised in cells to coordinate planar cell polarity in epithelial tissues and also to regulate morphogenetic movements in embryos. A well‐studied intracellular Wnt signal transduction mechanism promotes stabilisation and nuclear localisation of the protein β‐catenin to regulate transcription of specific target genes by interacting with deoxyribonucleic acid (DNA) ‐binding transcription factor proteins, such as the TCF/LEF proteins. Key Concepts: Wnt signalling functions in the embryo, to regulate stem cells and in disease such as cancer. Wnt signalling mechanisms regulate important cellular processes, such as cell fate specification, cell proliferation, cell differentiation, axon guidance and morphogenesis. Wnt proteins are lipid‐modified secreted signals. Frizzled proteins function as cell membrane receptors for Wnt signals. Wnt/Frizzled signalling activates a network of diverse intracellular signal transduction pathways. One conserved branch of Wnt signal transduction causes stabilisation and nuclear localisation of the protein β‐catenin. Nuclear β‐catenin regulates transcription of specific target genes by interacting with DNA‐binding proteins, such as TCF/LEF proteins. Other, β‐catenin‐independent Wnt signal transduction mechanisms also regulate the cytoskeleton and planar cell polarity. Feedback regulation and cross‐regulation between different Wnt signal transduction branches is characteristic of Wnt signalling.

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Wnt Signal Production, Secretion, and Diffusion

Cited by 3 publications

References 82 publications

The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators

The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators

Wnt signaling in the heart fields: Variations on a common theme

Cell‐to‐Cell Signalling in Development: Wnt Signalling

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