The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T.; Cousin, Hélène; Kleino, Iivari; Steinbeißer, Herbert; Alfandari, Dominique

doi:10.1242/jcs.163063

Cited by 11 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead, ADAMs 10 and 17, two somatic ADAMs, are known to interact with tetraspanins and nonproteolytic members of the Rhomboid family (iRhoms), respectively, which regulate the trafficking, stability and activity of these ADAMs (Adrain et al, 2012;Dornier et al, 2012;Haining et al, 2012;Matthews et al, 2017;McIlwain et al, 2012). The activity of Xenopus ADAM13 has also been shown to be regulated by other proteins, such as PACSIN2 and XFz4 (Abbruzzese et al, 2015;Cousin et al, 2000). In the current study, we observed a protective effect of ADAM19 towards ADAM13, which underlies the in vivo function of ADAM19 in NC specification.…”

Section: Discussionmentioning

confidence: 99%

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13

Perfetto

Neuner

et al. 2018

Development

Self Cite

View full text Add to dashboard Cite

During vertebrate gastrulation, canonical Wnt signaling induces the formation of neural plate border (NPB). Wnt is also thought to be required for the subsequent specification of neural crest (NC) lineage at the NPB, but the direct evidence is lacking. We found previously that the disintegrin metalloproteinase ADAM13 is required for Wnt activation and NC induction in Here, we report that knockdown of ADAM13 or its close paralog ADAM19 severely downregulates Wnt activity at the NPB, inhibiting NC specification without affecting earlier NPB formation. Surprisingly, ADAM19 functions nonproteolytically in NC specification by interacting with ADAM13 and inhibiting its proteasomal degradation. Ectopic expression of stabilized ADAM13 mutants that function independently of ADAM19 can induce the NC marker/specifier in the future epidermis via Wnt signaling. These results unveil the essential roles of a novel protease-protease interaction in regulating a distinct wave of Wnt signaling, which directly specifies the NC lineage.

show abstract

Section: Discussionmentioning

confidence: 99%

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13

Perfetto

Neuner

et al. 2018

Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, our result also suggests that when CIL needs to be reduced, for example to invade tissues that may express cadherin-11, ADAM13 can perform this function rapidly. Given that the proteolytic activity of ADAM13 is inhibited by Fz4 in the CNC (Abbruzzese et al, 2015), this protein could act as a switch to control cadherin-11 cleavage at various phases of CNC development and as such finely tune the intensity of CIL.…”

Section: Discussionmentioning

confidence: 99%

“…All constructs were transcribed in vitro into mRNA according to manufacturer's description (Ambion Inc.). in vivo CNC migration assays by targeted injection of a fluorescent lineage tracer were performed as previously published (Abbruzzese et al, 2014; Abbruzzese et al, 2015; Cousin et al, 2011; Cousin et al, 2012). Eight-cell stage embryos were injected into the D1 blastomere with 333 pg of RFP-flag mRNA, plus 333 pg of all cadherin-11 constructs for overexpression assays.…”

Section: Methodsmentioning

confidence: 99%

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

Abbruzzese

Becker

Kashef

et al. 2016

Developmental Biology

Self Cite

View full text Add to dashboard Cite

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo.

show abstract

“…Of the frizzled receptor family members, frizzled-4 has previously been shown to be of particular interest with respect to its role in the regulation of stem cell maintenance, neuroprotection, and cell migration in the CNS [ 19 – 21 ]. In the present study, we examined the expression of this Wnt receptor in the enteric nervous system of infants by immunohistochemistry, RT-PCR, and flow cytometry analysis.…”

Section: Introductionmentioning

confidence: 99%

Expression of the Wnt Receptor Frizzled‐4 in the Human Enteric Nervous System of Infants

Nothelfer

Obermayr

Belz

et al. 2015

Stem Cells International

View full text Add to dashboard Cite

The Wnt signalling pathway plays a crucial role in the development of the nervous system. This signalling cascade is initiated upon binding of the secreted Wnt ligand to a member of the family of frizzled receptors. In the present study, we analysed the presence of frizzled-4 in the enteric nervous system of human infants. Frizzled-4 could be identified by immunohistochemistry in a subpopulation of enteric neuronal and glial cells in the small and large intestine. Detection of frizzled-4 in the tunica muscularis by RT-PCR confirmed this receptor's expression on the mRNA level. Interestingly, we observed distinct cell populations that co-expressed frizzled-4 with the intermediate filament protein nestin and the neurotrophin receptor p75NTR, which have been reported to be expressed in neural progenitor cells. Flow cytometry analysis revealed that 60% of p75NTR positive cells of the tunica muscularis were positive for frizzled-4. Additionally, in pathological samples of Hirschsprung's disease, the expression of this Wnt receptor correlated with the number of myenteric ganglion cells and decreased from normoganglionic to aganglionic areas of large intestine. The expression pattern of frizzled-4 indicates that this Wnt receptor could be involved in postnatal development and/or function of the enteric nervous system.

show abstract

The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

Cited by 11 publications

References 35 publications

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

Expression of the Wnt Receptor Frizzled‐4 in the Human Enteric Nervous System of Infants

Contact Info

Product

Resources

About