ADAM proteases: ligand processing and modulation of the Notch pathway

Żółkiewska, Anna

doi:10.1007/s00018-008-7586-4

Cited by 83 publications

(64 citation statements)

References 104 publications

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“…Because Adam10 has many known substrates besides Notch, it is possible that the pathway through Adam10, Notch, and Foxi1 is not linear. Although results from transgenic models suggest that Adam10 serves as the key S2 cleavage enzyme for Notch in vivo, it is still possible that other enzymes, especially other Adams (such as Adam17), 23 may provide some compensatory function in the absence of Adam10, leading to the milder phenotypes in Adam10 mutants than expected. In addition, in the Xenopus skin, where Notch signaling inhibition increased the proton secreting intercalated-like cell types, this increase was primarily in type B IC-like cells and not as much in the type A IC-like cells.…”

Section: Discussionmentioning

confidence: 99%

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

Guo

Wang²,

Tripathi³

et al. 2015

Journal of the American Society of Nephrology

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A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane-anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2) + principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1.

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Section: Discussionmentioning

confidence: 99%

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

Guo

Wang²,

Tripathi³

et al. 2015

Journal of the American Society of Nephrology

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“…À/À keratinocytes regulate Notch1 activation through ADAM17/TACE To investigate the mechanism of precocious keratinocyte differentiation through Notch1 activation, we characterized the role of the metalloproteinase TACE, which cleaves and activates Notch1 (36 papillomas showed higher levels of TACE activity than uPAR þ/þ keratinocytes (Figs. 7A and B).…”

Section: Uparmentioning

confidence: 99%

Urokinase Receptor Promotes Skin Tumor Formation by Preventing Epithelial Cell Activation of Notch1

et al. 2015

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“…E-mail: kmatsuno@bio.sci.osaka-u.ac.jp age) (Brou et al, 2000;Mumm et al, 2000;Lieber et al, 2002). This cleavage removes most of the Notch extracellular domain and produces a membrane-tethered form of the Notch intracellular domain (NEXT) (Zolkiewska, 2008). Subsequently, NEXT is cleaved within its transmembrane domain by γ-secretase (the S3 cleavage), which liberates the intracellular domain, termed NICD (De Strooper et al, 1999;Struhl and Greenwald, 1999;Ye et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Loss- and gain-of-function analyses of <i>vacuolar protein sorting 2</i> in Notch signaling of <i>Drosophila melanogaster</i>

et al. 2013

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Notch signaling is an evolutionarily conserved mechanism that controls many cell-fate specifications through local cell-cell interactions. The core mechanisms of Notch activation and its subsequent intracellular signaling are well understood. Various cellular functions are required for the activation and regulation of Notch signaling. Among them, the endocytosis of Notch and its ligands is important for the activation and suppression of Notch signaling. The endosomal sorting complex required for transport (ESCRT) proteins are required to sort ubiquitinated membrane proteins, such as Notch, into early endosomes. A loss-of-function allele of vacuolar protein sorting 2 (vps2), which encodes a component of ESCRT-III, has been reported. However, this vps2 mutant still produces the N-terminal half of the protein, and its phenotypes were studied in only a few organs. Here, we generated the first null mutant allele of Drosophila vps2, designated vps2 2 , to better understand the function of this gene. In Drosophila wing imaginal discs homozygous for the vps2 2 allele, early endosomes and multivesicular bodies (MVBs) were enlarged, and Notch and Delta accumulated inside them. As reported for the previous vps2 mutant, the epithelium grew excessively under this condition. We further studied the roles of vps2 by RNA interferenceknockdown. These experiments revealed that a partial reduction of vps2 attenuated Notch signaling; in contrast, the loss-of-function vps2 mutant is reported to up-regulate the Notch signaling in eye imaginal disc cells. These results suggest that Notch signaling can be up-or down-regulated, depending on the level of vps2 expression. Finally, we found that vps2 overexpression also resulted in earlyendosome enlargement and the accumulation of Notch and Delta. In these cells, a portion of the Vps2 protein was detected in MVBs and colocalized with Notch. These data indicate that the expression of vps2 must be precisely regulated to maintain the normal structure of early endosomes.

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ADAM proteases: ligand processing and modulation of the Notch pathway

Cited by 83 publications

References 104 publications

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

Urokinase Receptor Promotes Skin Tumor Formation by Preventing Epithelial Cell Activation of Notch1

Loss- and gain-of-function analyses of <i>vacuolar protein sorting 2</i> in Notch signaling of <i>Drosophila melanogaster</i>

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