Calcium-activated chloride channel regulator 1 (CLCA1) forms non-covalent oligomers in colonic mucus and has mucin 2-processing properties.

作者: Elisabeth E. L. Nyström , Liisa Arike , Erik Ehrencrona , Gunnar C. Hansson , Malin E. V. Johansson

DOI: 10.1074/JBC.RA119.009940

关键词:

摘要: Calcium-activated chloride channel regulator 1 (CLCA1) is one of the major nonmucin proteins found in intestinal mucus. It part a larger family CLCA that share highly conserved features and domain architectures. The arrangement similar to belonging ADAM (a disintegrin metalloproteinase) family, known process extracellular matrix proteins. Therefore, CLCA1 an interesting candidate search for proteases Here, we investigated CLCA1's biochemical properties both vitro mucus from mouse human colon biopsy samples. Using immunoblotting with CLCA1-specific antibodies recombinant proteins, observed C-terminal self-cleavage product forms disulfide-linked dimer noncovalently interacts N-terminal CLCA1, which further form oligomers. We also characterized second, more catalytically active, encompassing catalytic together its von Willebrand type A (VWA). This fragment was unstable but could be identified freshly prepared Furthermore, can cleave structural component MUC2. propose regulates thereby takes regulation processing.

参考文章(43)
Jessica M Holmén Larsson, Hasse Karlsson, Henrik Sjövall, Gunnar C Hansson, A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. Glycobiology. ,vol. 19, pp. 756- 766 ,(2009) , 10.1093/GLYCOB/CWP048
Martine Hamann, Adele Gibson, Noel Davies, Amanda Jowett, Jean Philippe Walhin, Leanne Partington, Karen Affleck, Derek Trezise, Martin Main, Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents. The Journal of Physiology. ,vol. 587, pp. 2255- 2274 ,(2009) , 10.1113/JPHYSIOL.2009.170159
Edy Y. Kim, Yael Alevy, Suzanne Swanson, Jennifer Tucker, Guaming Huang, Eugene Agapov, Thomas E. Phillips, Maria E. Fuentes, Antonio Iglesias, Dee Aud, John D. Allard, Karim Dabbagh, Gary Peltz, Michael J. Holtzman, Anand C. Patel, Jeffrey D. Morton, Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members Physiological Genomics. ,vol. 25, pp. 502- 513 ,(2006) , 10.1152/PHYSIOLGENOMICS.00321.2005
Malin E V Johansson, Jenny K Gustafsson, Jessica Holmén-Larsson, Karolina S Jabbar, Lijun Xia, Hua Xu, Fayez K Ghishan, Frederic A Carvalho, Andrew T Gewirtz, Henrik Sjövall, Gunnar C Hansson, Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis Gut. ,vol. 63, pp. 281- 291 ,(2014) , 10.1136/GUTJNL-2012-303207
Judith M White, ADAMs: modulators of cell-cell and cell-matrix interactions. Current Opinion in Cell Biology. ,vol. 15, pp. 598- 606 ,(2003) , 10.1016/J.CEB.2003.08.001
Monica Sala-Rabanal, Zeynep Yurtsever, Colin G Nichols, Tom J Brett, Secreted CLCA1 modulates TMEM16A to activate Ca2+-dependent chloride currents in human cells eLife. ,vol. 4, ,(2015) , 10.7554/ELIFE.05875
Franck Brouillard, Noura Bensalem, Alexandre Hinzpeter, Danielle Tondelier, Stéphanie Trudel, Achim D. Gruber, Mario Ollero, Aleksander Edelman, Blue Native/SDS-PAGE Analysis Reveals Reduced Expression of the mClCA3 Protein in Cystic Fibrosis Knock-out Mice Molecular & Cellular Proteomics. ,vol. 4, pp. 1762- 1775 ,(2005) , 10.1074/MCP.M500098-MCP200
Lars Mundhenk, Marwan Alfalah, Randolph C. Elble, Bendicht U. Pauli, Hassan Y. Naim, Achim D. Gruber, Both cleavage products of the mCLCA3 protein are secreted soluble proteins. Journal of Biological Chemistry. ,vol. 281, pp. 30072- 30080 ,(2006) , 10.1074/JBC.M606489200
D. Ambort, M. E. V. Johansson, J. K. Gustafsson, H. E. Nilsson, A. Ermund, B. R. Johansson, P. J. B. Koeck, H. Hebert, G. C. Hansson, Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin Proceedings of the National Academy of Sciences of the United States of America. ,vol. 109, pp. 5645- 5650 ,(2012) , 10.1073/PNAS.1120269109
Ina Leverkoehne, Achim D. Gruber, The Murine mCLCA3 (Alias gob-5) Protein Is Located in the Mucin Granule Membranes of Intestinal, Respiratory, and Uterine Goblet Cells Journal of Histochemistry and Cytochemistry. ,vol. 50, pp. 829- 838 ,(2002) , 10.1177/002215540205000609