AGR2, an Endoplasmic Reticulum Protein, Is Secreted into the Gastrointestinal Mucus

被引:61
作者
Bergstrom, Joakim H. [1 ]
Berg, Katarina A. [1 ]
Rodriguez-Pineiro, Ana M. [1 ]
Stecher, Baerbel [2 ]
Johansson, Malin E. V. [1 ]
Hansson, Gunnar C. [1 ]
机构
[1] Univ Gothenburg, Dept Med Biochem, Gothenburg, Sweden
[2] Ludwig Maximilians Univ Munchen, Max von Pettenkofer Inst Hyg & Med Microbiol, Munich, Germany
基金
瑞典研究理事会;
关键词
ANTERIOR GRADIENT 2; SMALL-INTESTINE; MOUSE STOMACH; MUCIN; LAYERS; GENE; HOMEOSTASIS; EXPRESSION; TERMINUS; DISEASE;
D O I
10.1371/journal.pone.0104186
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The MUC2 mucin is the major constituent of the two mucus layers in colon. Mice lacking the disulfide isomerase-like protein Agr2 have been shown to be more susceptible to colon inflammation. The Agr2(-/-) mice have less filled goblet cells and were now shown to have a poorly developed inner colon mucus layer. We could not show AGR2 covalently bound to recombinant MUC2 N- and C-termini as have previously been suggested. We found relatively high concentrations of Agr2 in secreted mucus throughout the murine gastrointestinal tract, suggesting that Agr2 may play extracellular roles. In tissue culture (CHO-K1) cells, AGR2 is normally not secreted. Replacement of the single Cys in AGR2 with Ser (C81S) allowed secretion, suggesting that modification of this Cys might provide a mechanism for circumventing the KTEL endoplasmic reticulum retention signal. In conclusion, these results suggest that AGR2 has both intracellular and extracellular effects in the intestine.
引用
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页数:8
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