scholarly journals Correction for Maretzky et al., iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding

2021 ◽  
Vol 118 (34) ◽  
pp. e2112652118
2012 ◽  
Vol 23 (10) ◽  
pp. 1964-1975 ◽  
Author(s):  
Hironao Nakayama ◽  
Shinji Fukuda ◽  
Hirofumi Inoue ◽  
Hisayo Nishida-Fukuda ◽  
Yuji Shirakata ◽  
...  

A disintegrin and metalloproteinase (ADAM) is a family of enzymes involved in ectodomain shedding of various membrane proteins. However, the molecular mechanism underlying substrate recognition by ADAMs remains unknown. In this study, we successfully captured and analyzed cell surface transient assemblies between the transmembrane amphiregulin precursor (proAREG) and ADAM17 during an early shedding phase, which enabled the identification of cell surface annexins as components of their shedding complex. Annexin family members annexin A2 (ANXA2), A8, and A9 interacted with proAREG and ADAM17 on the cell surface. Shedding of proAREG was increased when ANXA2 was knocked down but decreased with ANXA8 and A9 knockdown, because of enhanced and impaired association with ADAM17, respectively. Knockdown of ANXA2 and A8 in primary keratinocytes altered wound-induced cell migration and ultraviolet B–induced phosphorylation of epidermal growth factor receptor (EGFR), suggesting that annexins play an essential role in the ADAM-mediated ectodomain shedding of EGFR ligands. On the basis of these data, we propose that annexins on the cell surface function as “shedding platform” proteins to determine the substrate selectivity of ADAM17, with possible therapeutic potential in ADAM-related diseases.


2013 ◽  
Vol 110 (28) ◽  
pp. 11433-11438 ◽  
Author(s):  
T. Maretzky ◽  
D. R. McIlwain ◽  
P. D. A. Issuree ◽  
X. Li ◽  
J. Malapeira ◽  
...  

2005 ◽  
Vol 4 (2) ◽  
pp. 258-267 ◽  
Author(s):  
Irina V. Balyasnikova ◽  
Zenda L. Woodman ◽  
Ronald F. Albrecht ◽  
Ramanathan Natesh ◽  
K. Ravi Acharya ◽  
...  

2021 ◽  
Vol 22 (6) ◽  
pp. 3012
Author(s):  
James I. Mitchell-White ◽  
Thomas Stockner ◽  
Nicholas Holliday ◽  
Stephen J. Briddon ◽  
Ian D. Kerr

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.


2021 ◽  
Vol 54 (5) ◽  
pp. 2079-2089
Author(s):  
Yaron Aviv ◽  
Esra Altay ◽  
Ofer Burg ◽  
Marcus Müller ◽  
Javid Rzayev ◽  
...  

2007 ◽  
Vol 73 (11) ◽  
pp. 3637-3644 ◽  
Author(s):  
Alberto Amaretti ◽  
Tatiana Bernardi ◽  
Elena Tamburini ◽  
Simona Zanoni ◽  
Mariella Lomma ◽  
...  

ABSTRACT The kinetics and the metabolism of Bifidobacterium adolescentis MB 239 growing on galactooligosaccharides (GOS), lactose, galactose, and glucose were investigated. An unstructured unsegregated model for growth in batch cultures was developed, and kinetic parameters were calculated with a recursive algorithm. The growth rate and cellular yield were highest on galactose, followed by lactose and GOS, and were lowest on glucose. Lactate, acetate, and ethanol yields allowed the calculation of carbon fluxes toward fermentation products. Distributions between two- and three-carbon products were similar on all the carbohydrates (55 and 45%, respectively), but ethanol yields were different on glucose, GOS, lactose, and galactose, in decreasing order of production. Based on the stoichiometry of the fructose-6-phosphate shunt and on the carbon distribution among the products, the ATP yield was calculated. The highest yield was obtained on galactose, while the yields were 5, 8, and 25% lower on lactose, GOS, and glucose, respectively. Therefore, a correspondence among ethanol production, low ATP yields, and low biomass production was established, demonstrating that carbohydrate preferences may result from different distributions of carbon fluxes through the fermentative pathway. During the fermentation of a GOS mixture, substrate selectivity based on the degree of polymerization was exhibited, since lactose and the trisaccharide were the first to be consumed, while a delay was observed until longer oligosaccharides were utilized. Throughout the growth on both lactose and GOS, galactose accumulated in the cultural broth, suggesting that β(1-4) galactosides can be hydrolyzed before they are taken up.


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