Helping Wingless take flight: how WNT proteins are secreted

Hausmann, George; Bänziger, Carla; Basler, Konrad

doi:10.1038/nrm2141

Cited by 130 publications

(106 citation statements)

References 59 publications

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“…Wls is a multipass membrane protein that spans the membrane seven or eight times, depending on whether the signal sequence is cleaved (15,16). However, the signals/motifs for internalization and endosomal sorting of Wls have not been identified.…”

Section: Loss Of Wls Results In Impairment Of Wnt Secretion and Defecmentioning

confidence: 99%

Identification of an Endocytosis Motif in an Intracellular Loop of Wntless Protein, Essential for Its Recycling and the Control of Wnt Protein Signaling

Gasnereau

Herr

Chia

et al. 2011

Journal of Biological Chemistry

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Background:The secretion of Wnt molecules is dependent on the multipass membrane-sorting receptor, Wntless. Results: A tyrosine-based internalization motif has been identified in an intracellular loop of Wntless. Conclusion: Endocytosis of Wntless is required for efficient secretion of Wnt signaling molecules. Significance: Defining the sorting signals and intracellular trafficking of Wntless is crucial to appreciate the regulation of Wnt secretion and development processes.

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Section: Loss Of Wls Results In Impairment Of Wnt Secretion and Defecmentioning

confidence: 99%

Identification of an Endocytosis Motif in an Intracellular Loop of Wntless Protein, Essential for Its Recycling and the Control of Wnt Protein Signaling

Gasnereau

Herr

Chia

et al. 2011

Journal of Biological Chemistry

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“…In 2003, Wnt3a was purified and the hydrophobic structure common for Wnt proteins was identified. 12,13 Functionally, because of their biochemical properties, Wnt ligands are short-range signaling molecules. 14 So far, 19 different Wnt ligands have been identified and structurally described.…”

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confidence: 99%

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Reuter

Beckert

Taube

2016

Laboratory Investigation

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Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

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“…Before initiating their effects on the signal-receiving cells, Wnt proteins undergo proper modification, sorting and secretion processes in the signalproducing cells (16)(17)(18)(19). Recent identification of Wntless (Wls/Evi/ Srt) (20)(21)(22), a regulator for Wnt production in Drosophila, has directed attention to the maturation, sorting and secretion processes in signal-producing cells.…”

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confidence: 99%

Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation

Jiang

Mirando

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

192

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Members of the Wnt family are secreted glycoproteins that trigger cellular signals essential for proper development of organisms. Cellular signaling induced by Wnt proteins is involved in diverse developmental processes and human diseases. Previous studies have generated an enormous wealth of knowledge on the events in signal-receiving cells. However, relatively little is known about the making of Wnt in signal-producing cells. Here, we describe that Gpr177, the mouse orthologue of Drosophila Wls, is expressed during formation of embryonic axes. Embryos with deficient Gpr177 exhibit defects in establishment of the body axis, a phenotype highly reminiscent to the loss of Wnt3. Although many different mammalian Wnt proteins are required for a wide range of developmental processes, the Wnt3 ablation exhibits the earliest developmental abnormality. This suggests that the Gpr177-mediated Wnt production cannot be substituted. As a direct target of Wnt, Gpr177 is activated by ␤-catenin and LEF/TCF-dependent transcription. This activation alters the cellular distributions of Gpr177 which binds to Wnt proteins and assists their sorting and secretion in a feedback regulatory mechanism. Our findings demonstrate that the loss of Gpr177 affects Wnt production in the signal-producing cells, leading to alterations of Wnt signaling in the signal-receiving cells. A reciprocal regulation of Wnt and Gpr177 is essential for the patterning of the anterior-posterior axis during mammalian development.A-P axis ͉ ␤-catenin ͉ developmental deformities ͉ primitive streak ͉ Wnt production

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Helping Wingless take flight: how WNT proteins are secreted

Cited by 130 publications

References 59 publications

Identification of an Endocytosis Motif in an Intracellular Loop of Wntless Protein, Essential for Its Recycling and the Control of Wnt Protein Signaling

Identification of an Endocytosis Motif in an Intracellular Loop of Wntless Protein, Essential for Its Recycling and the Control of Wnt Protein Signaling

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation

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