Alternative Wnt Pathways and Receptors

Amerongen, Renée van

doi:10.1101/cshperspect.a007914

Cited by 181 publications

(158 citation statements)

References 199 publications

(212 reference statements)

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“…How might both increased and decreased levels of the Dlp co-receptor yield increased FNI pathway signal transduction? Regulation of Wnt signaling interactions ligands, co-receptors and receptors is managed at many levels (van Amerongen, 2012). The 'Wg exchange factor model' (Yan et al, 2009) provides a mechanistic framework for understanding the suppressive interactions of Mmp.…”

Section: Discussionmentioning

confidence: 99%

Two matrix metalloproteinase classes reciprocally regulate synaptogenesis

et al. 2015

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Synaptogenesis requires orchestrated intercellular communication between synaptic partners, with trans-synaptic signals necessarily traversing the extracellular synaptomatrix separating presynaptic and postsynaptic cells. Extracellular matrix metalloproteinases (Mmps) regulated by secreted tissue inhibitors of metalloproteinases (Timps), cleave secreted and membrane-associated targets to sculpt the extracellular environment and modulate intercellular signaling. Here, we test the roles of Mmp at the neuromuscular junction (NMJ) model synapse in the reductionist Drosophila system, which contains just two Mmps (secreted Mmp1 and GPI-anchored Mmp2) and one secreted Timp. We found that all three matrix metalloproteome components co-dependently localize in the synaptomatrix and show that both Mmp1 and Mmp2 independently restrict synapse morphogenesis and functional differentiation. Surprisingly, either dual knockdown or simultaneous inhibition of the two Mmp classes together restores normal synapse development, identifying a reciprocal suppression mechanism. The two Mmp classes coregulate a Wnt trans-synaptic signaling pathway modulating structural and functional synaptogenesis, including the GPIanchored heparan sulfate proteoglycan (HSPG) Wnt co-receptor Dally-like protein (Dlp), cognate receptor Frizzled-2 (Frz2) and Wingless (Wg) ligand. Loss of either Mmp1 or Mmp2 reciprocally misregulates Dlp at the synapse, with normal signaling restored by coremoval of both Mmp classes. Correcting Wnt co-receptor Dlp levels in both Mmp mutants prevents structural and functional synaptogenic defects. Taken together, these results identify an Mmp mechanism that fine-tunes HSPG co-receptor function to modulate Wnt signaling to coordinate synapse structural and functional development.

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Section: Discussionmentioning

confidence: 99%

Two matrix metalloproteinase classes reciprocally regulate synaptogenesis

et al. 2015

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“…Ror2 elicits multiple functions in Wnt signaling (see also Fig. 1): (1) Ror2 interacts with Frizzled (Fzd) receptors and the intracellular protein Dishevelled (Dvl) to activate Wnt/PCP signaling, 42,43 (2) Ror2 is able to antagonize Wnt/b-Catenin signaling in cells and embryonic tissues, 44,45 and (3) Ror2 activates a PI3K-dependent signaling cascade that transcriptionally regulates expression of paraxial protocadherin (PAPC). 46,47 PAPC and the closely related PCNS are the two paralogs of Protocadherin 8 (PDCH8) in Xenopus laevis.…”

Section: Wnt Signalingmentioning

confidence: 99%

Signaling pathways and tissue interactions in neural plate border formation

Schille

Schambony

2017

Neurogenesis

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The neural crest is a transient cell population that gives rise to various cell types of multiple tissues and organs in the vertebrate embryo. Neural crest cells arise from the neural plate border, a region localized at the lateral borders of the prospective neural plate. Temporally and spatially coordinated interaction with the adjacent tissues, the non-neural ectoderm, the neural plate and the prospective dorsolateral mesoderm, is required for neural plate border specification. Signaling molecules, namely BMP, Wnt and FGF ligands and corresponding antagonists are derived from these tissues and interact to induce the expression of neural plate border specific genes. The present mini-review focuses on the current understanding of how the NPB territory is formed and accentuates the need for coordinated interaction of BMP and Wnt signaling pathways and precise tissue communication that are required for the definition of the prospective NC in the competent ectoderm.

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“…Canonical Wnt signaling involves activation of the ␤-catenin signaling pathway. Non-canonical Wnt signaling involves other pathways including planar cell polarity and Ca 2ϩ pathways (10,12,13). Wnt3a is the prototypical ligand that induces canonical signaling, whereas Wnt5a has mostly been associated with non-canonical signaling.…”

mentioning

confidence: 99%

Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury

Nakamura

Sano

Fuster

et al. 2016

Journal of Biological Chemistry

111

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Wnt signaling has diverse actions in cardiovascular development and disease processes. Secreted frizzled-related protein 5 (Sfrp5) has been shown to function as an extracellular inhibitor of non-canonical Wnt signaling that is expressed at relatively high levels in white adipose tissue. The aim of this study was to investigate the role of Sfrp5 in the heart under ischemic stress. Sfrp5 KO and WT mice were subjected to ischemia/reperfusion (I/R). Although Sfrp5-KO mice exhibited no detectable phenotype when compared with WT control at baseline, they displayed larger infarct sizes, enhanced cardiac myocyte apoptosis, and diminished cardiac function following I/R. The ischemic lesions of Sfrp5-KO mice had greater infiltration of Wnt5a-positive macrophages and greater inflammatory cytokine and chemokine gene expression when compared with WT mice. In bone marrow-derived macrophages, Wnt5a promoted JNK activation and increased inflammatory gene expression, whereas treatment with Sfrp5 blocked these effects. These results indicate that Sfrp5 functions to antagonize inflammatory responses after I/R in the heart, possibly through a mechanism involving non-canonical Wnt5a/JNK signaling.Inflammation is widely recognized to be involved in the pathogenesis, severity, and outcome of ischemic heart disease (1). Obesity is thought to contribute to cardiovascular disorders, at least in part, through the systemic release of pro-inflammatory adipokines by dysfunctional white adipose tissue (WAT) 2 (2, 3). Inflammation has complex roles in both adaptive healing process following infarction as well as in the maladaptive processes that contribute to heart failure (4 -7), and the acute healing and eventual outcome of ischemic myocardial injury are dependent upon the appropriately choreographed regulation of numerous pro-and anti-inflammatory modulators. In this regard, immune modulators produced by adipose tissue can either facilitate or impair the myocardial healing process, depending on the status of adipose tissue function and the composition of its inflammatory secretome (3,8,9). Thus, a better understanding of the links between obesity-mediated inflammatory processes and post-infarct remodeling of the heart is warranted.At the cellular level, inflammatory processes are tightly orchestrated by secreted signaling molecules that bind to specific cell surface receptors and activate intracellular signaling pathways. Signaling by Wnt ligands is a major regulator of several biological processes, but its roles in modulating inflammatory responses are relatively understudied. The 19 Wnt family proteins contain cysteine-rich domains and activate signaling by binding to one or more of the 10 frizzled family receptors (10). Wnt signaling can be classified as canonical or a noncanonical (10, 11). Canonical Wnt signaling involves activation of the ␤-catenin signaling pathway. Non-canonical Wnt signaling involves other pathways including planar cell polarity and Ca 2ϩ pathways (10, 12, 13). Wnt3a is the prototypical ligand that induces canonica...

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Alternative Wnt Pathways and Receptors

Cited by 181 publications

References 199 publications

Two matrix metalloproteinase classes reciprocally regulate synaptogenesis

Two matrix metalloproteinase classes reciprocally regulate synaptogenesis

Signaling pathways and tissue interactions in neural plate border formation

Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury

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