The RYK Receptor Family

Halford, Michael M.; Macheda, Maria L.; Stacker, Steven A.

doi:10.1007/978-3-319-11888-8_15

Cited by 8 publications

(11 citation statements)

References 176 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As RYK is known to modulate both β-catenin−dependent and β-catenin−independent signaling (18,19), we first examined whether RYK participates in WNT/β-catenin signaling, by crossing Ryk SL mutant mice with the TOPGAL reporter line. While β-catenin−dependent transcription was active in the airway epithelium of wild-type lungs, it was dramatically decreased in Ryk SL/SL airway epithelium (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

Kim

Yin

Nakamichi

et al. 2019

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

View full text Add to dashboard Cite

Goblet cell metaplasia and mucus hypersecretion are observed in many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the regulation of goblet cell differentiation remains unclear. Here, we identify a regulator of this process in anN-ethyl-N-nitrosourea (ENU) screen for modulators of postnatal lung development;Rykmutant mice exhibit lung inflammation, goblet cell hyperplasia, and mucus hypersecretion. RYK functions as a WNT coreceptor, and, in the developing lung, we observed high RYK expression in airway epithelial cells and moderate expression in mesenchymal cells as well as in alveolar epithelial cells. From transcriptomic analyses and follow-up studies, we found decreased WNT/β-catenin signaling activity in the mutant lung epithelium. Epithelial-specificRykdeletion causes goblet cell hyperplasia and mucus hypersecretion but not inflammation, while club cell-specificRykdeletion in adult stages leads to goblet cell hyperplasia and mucus hypersecretion during regeneration. We also found that the airway epithelium of COPD patients often displays goblet cell metaplastic foci, as well as reduced RYK expression. Altogether, our findings reveal that RYK plays important roles in maintaining the balance between airway epithelial cell populations during development and repair, and that defects in RYK expression or function may contribute to the pathogenesis of human lung diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Related to tyrosine kinase (RYK), a WNT coreceptor, belongs to the atypical receptor tyrosine kinase family (18,19). The functions of RYK have been studied in several model organisms, including Drosophila (20), zebrafish (21), Xenopus (22), and mouse (23).…”

mentioning

confidence: 99%

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

Kim

Yin

Nakamichi

et al. 2019

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

View full text Add to dashboard Cite

show abstract

“…The specific pathway activated by WNT5A in the RA FLS required the RYK receptor. RYK is an atypical receptor tyrosine kinase due to its inactive tyrosine kinase domain (58). It has been extensively studied in the development of nervous systems where it is important for establishing planar polarity during neural tube development and neuronal migration into the expanding cortical plate (16).…”

Section: Discussionmentioning

confidence: 99%

“…It has been extensively studied in the development of nervous systems where it is important for establishing planar polarity during neural tube development and neuronal migration into the expanding cortical plate (16). However, it participates in many other systems as revealed in the Ryk loss-offunction mice with skeletal, craniofacial and cardiac abnormalities many of them overlapping with the observed in the Wnt5a null mice (58). This pathway of WNT5A migration promotion was in contrast with the followed by some other systems that require ROR2.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Non-Canonical WNT5A Signaling Through RYK Contributes to Aggressive Phenotype of the Rheumatoid Fibroblast-Like Synoviocytes

et al. 2020

View full text Add to dashboard Cite

We hypothesized that WNT5A could contribute to the enhanced migration and invasiveness of rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), which is one of the incompletely understood aspects of the RA FLS aggressive phenotype. This hypothesis is based on the previous evidence of a WNT5A role in both, RA and cell migration. Migration and invasion of RA FLS were assessed after incubation with recombinant Wnt5a (rWnt5a) or silencing of the endogenous WNT5A expression. The expression of WNT5A, WNT receptors, cytokines, chemokines, and metalloproteinases was quantified with RT-PCR. The WNT pathway was explored with gene silencing, antibody and pharmacological inhibition followed by migration assays and phosphoprotein western blots. Here, we reported that rWnt5a promoted migration and invasion of RA FLS, whereas knockdown of the endogenous WNT5A reduced them. These effects were specific to the RA FLS since they were not observed in FLS from osteoarthritis (OA) patients. Also, rWnt5a induced the expression of IL6, IL8, CCL2, CXCL5, MMP1, MMP3, MMP9, and MMP13 from baseline or potentiating the TNF induction, WNT5A signaling required the RYK receptor and was mediated through the WNT/Ca 2+ and the ROCK pathway. These pathways involved the RYK and ROCK dependent activation of the p38, ERK, AKT, and GSK3b kinases, but not the activation of JNK. Together these findings indicate that WNT5A contributes to the enhanced migration and invasiveness of RA FLS through RYK and the specific activation of ROCK and downstream kinases.

show abstract

The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis

Lanoue

Langford

White

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation. We demonstrate that loss of Ryk in mouse hippocampal and cortical neurons promotes excessive dendrite growth and branching in vitro. Conversely, overexpression of wildtype Ryk restricts these processes, confirming that Ryk acts to restrain dendrite arborisation. Furthermore, we identify a hitherto uncharacterized membrane proximal subdomain crucial for Ryk-mediated suppression of dendrite morphogenesis, suggesting that it may act through a novel signalling pathway to constrain dendrite complexity. We also demonstrate that Ryk performs a similar function in vivo as Ryk haploinsufficient postnatal animals exhibit excessive dendrite growth and branching in layer 2/3 pyramidal neurons of the somatosensory cortex. These findings reveal an essential role for Ryk in regulating dendrite complexity and raise the intriguing possibility that it may influence neural plasticity by modifying dendritic structure.

show abstract

The RYK Receptor Family

Cited by 8 publications

References 176 publications

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

Non-Canonical WNT5A Signaling Through RYK Contributes to Aggressive Phenotype of the Rheumatoid Fibroblast-Like Synoviocytes

The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis

Contact Info

Product

Resources

About