ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes

Shi, Feng; Mendrola, Jeannine M.; Sheetz, Joshua B.; Wu, Neo; Sommer, Anselm; Speer, Kelsey F.; Noordermeer, Jasprina N.; Kan, Zhong-yuan; Perry, Kay; Englander, S. Walter; Stayrook, Steven E.; Fradkin, Lee G.; Lemmon, Mark A.

doi:10.1016/j.celrep.2021.109834

Cited by 22 publications

(15 citation statements)

References 100 publications

(158 reference statements)

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“…18 Among these, Axin2 seems to be a well-preserved target across cell types and species. 19 Frizzled, however, have also been reported to associate with other co-receptors, such as the Receptor Tyrosine Kinase-like Orphan Receptor 2 (ROR2) and the Related to Receptor Tyrosine Kinase (RYK), 20,21 promoting the activation of less characterised signalling cascades. These have been grouped under the name of βcatenin-independent pathways.…”

Section: The Wnt Signallingmentioning

confidence: 99%

Wnt signalling in the articular cartilage: A matter of balance

Gill

McCormick

Sochart

et al. 2023

Int J Experimental Path

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Degradation of the articular cartilage is a hallmark of osteoarthritis, a progressive and chronic musculoskeletal condition, affecting millions of people worldwide. The activation of several signalling cascades is altered during disease development: among them, the Wnt signalling plays a pivotal role in the maintenance of tissue homeostasis. Increasing evidence is showing that its activation needs to be maintained within a certain range to avoid the triggering of degenerative mechanisms. In this review, we summarise our current knowledge about how a balanced activation of the Wnt signalling is maintained in the articular cartilage, with a particular focus on receptor‐mediated mechanisms.

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Section: The Wnt Signallingmentioning

confidence: 99%

Wnt signalling in the articular cartilage: A matter of balance

Gill

McCormick

Sochart

et al. 2023

Int J Experimental Path

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“…Wnt5A belongs to a family of glycoprotein ligands that initiate signaling upon binding to the Frizzled and ROR/Ryk families of transmembrane cell surface receptors. While Frizzleds resemble the heterotrimeric G protein-coupled receptors, ROR1, ROR2, and Ryk resemble tyrosine kinases ( 1 – 3 ). Wnt-Frizzled/ROR/Ryk signaling has long been known to be crucial for tissue patterning and organism development ( 4 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Wnt5A Signaling Regulates Gut Bacterial Survival and T Cell Homeostasis

Sengupta

Jati

Maity

et al. 2022

mSphere

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Gut commensal bacterial diversity and T cell homeostasis are crucial entities of the host innate immune network, yet the molecular details of host-directed signaling pathways that sustain the steady state of gut bacterial colonization and T cell activation remain unclear. Here, we describe the protective role of a Wnt5A-actin axis in the survival of several gut bacterial commensals and its necessity in shaping gut bacterial colonization and the associated T cell repertoire.

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“…Wnt5A belongs to the19member family of glycoprotein ligands that initiate signaling upon binding to the Frizzled and ROR/Ryk families of transmembrane cell surface receptors. While Frizzleds, about 12 in number, resemble the heterotrimeric G protein coupled receptors, ROR1, ROR2 and Ryk resemble tyrosine kinases (1)(2)(3). Wnt -Frizzled/ROR/Ryk signaling has long been known to be crucial for tissue patterning and organism development (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Wnt5A Signaling Regulates Gut Bacterial Survival and T cell Homeostasis

Sengupta

Jati

Maity

et al. 2022

Preprint

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In light of the demonstrated antagonism of Wnt5A signaling toward the growth of several bacterial pathogens, it was important to study the influence of Wnt5A on gut resident bacteria, and its outcome. Here we demonstrate that in contrast to inhibiting the survival of the established gut pathogen Salmonella enterica, Wnt5A clearly promotes the survival of the common gut commensals Enterococcus faecalis and Lactobacillus rhamnosus within macrophages through a self-perpetuating Wnt5A-Actin axis. A Wnt5A – Actin axis furthermore regulates the subsistence of the natural bacterial population of the Peyer’s patches, as is evident from the diminution in the countable bacterial colony forming units therein through the application of Wnt5A signaling and actin assembly inhibitors. Wnt5A dependency of the gut resident bacterial population is also manifested in the notable difference between the bacterial diversities associated with the feces and Peyer’s patches of Wnt5A heterozygous mice, which lack a functional copy of the Wnt5A gene, and the wild type counterparts. Alterations in gut commensal bacterial population resulting from either the lack of a copy of the Wnt5A gene or inhibitor mediated attenuation of Wnt5A signaling correlate with significantly different ratios of regulatory vs. activated CD4 T cells associated with the Peyer’s patches. Taken together, our study reveals the importance of Wnt5A signaling in shaping the gut commensal bacterial population and the T cell repertoire linked to it, thus unveiling a crucial control device for the maintenance of gut bacterial diversity and T cell homeostasis.Significance StatementGut commensal bacterial diversity and T cell homeostasis are crucial entities of the host innate immune network. Yet molecular details of host directed signaling pathways that sustain the steady state of gut bacterial colonization and T cell activation remain unclear. Here we describe the protective role of a Wnt5A-Actin axis in the survival of several gut bacterial commensals, and its importance in shaping gut bacterial colonization and the associated T cell repertoire. This study opens up new avenues of investigation into the role of the Wnt5A-Actin axis in protection of the gut from dysbiosis related inflammatory disorders.

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ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes

Cited by 22 publications

References 100 publications

Wnt signalling in the articular cartilage: A matter of balance

Wnt signalling in the articular cartilage: A matter of balance

Wnt5A Signaling Regulates Gut Bacterial Survival and T Cell Homeostasis

Wnt5A Signaling Regulates Gut Bacterial Survival and T cell Homeostasis

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