Dataset Information

Ileum and colon goblet cell proteome

ABSTRACT: This study is a comparative proteomics study of FACS sorted Muc2 expressing and non expressing cells in mouse ileum and colon.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Goblet Cell, Epithelial Cell, Colon, Ileum

SUBMITTER: Liisa Arike

LAB HEAD: Liisa Arike

PROVIDER: PXD011527 | Pride | 2021-04-19

REPOSITORIES: Pride

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Publications

Transglutaminase 3 crosslinks the secreted gel-forming mucus component Mucin-2 and stabilizes the colonic mucus layer.

Sharpen Jack D A JDA Dolan Brendan B Nyström Elisabeth E L EEL Birchenough George M H GMH Arike Liisa L Martinez-Abad Beatriz B Johansson Malin E V MEV Hansson Gunnar C GC Recktenwald Christian V CV

Nature communications 20220111 1

The colonic mucus layer is organized as a two-layered system providing a physical barrier against pathogens and simultaneously harboring the commensal flora. The factors contributing to the organization of this gel network are not well understood. In this study, the impact of transglutaminase activity on this architecture was analyzed. Here, we show that transglutaminase TGM3 is the major transglutaminase-isoform expressed and synthesized in the colon. Furthermore, intrinsic extracellular transg ...[more]

PMID: 35017479

Publication: 1/2

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Project description:In this study we compared the intestinal mucus phenotype of Clca1-deficient (Clca1-/-) mice and wild-type (WT) controls. The human CLCA1 (chloride channel regulator, calcium-activated) and its murine ortholog mouse CLCA1 (formerly known as CLCA3) are secreted proteins which have been linked to human respiratory diseases such as asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) as well as to the corresponding murine models of these diseases. Common, disease severity-related features are goblet cell hyperplasia, mucus overproduction and disturbed clearance. Neutralization of mouse CLCA1 ameliorates the symptoms in the asthmatic mouse model and restoration of the decreased mouse CLCA1 protein level in a CF mouse model ameliorates the intestinal CF lesions, pointing toward these proteins being potential therapeutic targets. The expression CLCA1 can be induced in airways but this protein is normally expressed and secreted by goblet cells of the intestinal tract in both human and mouse together with the intestinal MUC2 mucin. This makes CLCA1 a major constituent of the extracellular intestinal mucus in which the MUC2 mucin is the main structural component. To study the possible further effects of murine CLCA1 deficiency on Muc2 and on other important components of the mucus, such as Agr2, Fcgbp, Klk and Zg16, a shotgun label-free proteomics study was performed which compared their relative abundance in the mucus layer, showing a tight and significant correlation between WT and Clca1-/- mucus proteins (Pearson r = 0.931, r2 = 0.868, p < 0.0001, based on 809 valid pairs). No significant differences in known mucus protein expression were observed. However, the abundance of CLCA1 in the mucus together with the domain structure suggests a structural role and other methods to reveal the function of these domains might shed light on the overall function in mucus. Because of its abundance in the mucus and the well preserved structure thought a long evolution together with mucus we still speculate that CLCA1 was developed to protect the expressing organism, although the threat is elusive.

Dataset Information

Ileum and colon goblet cell proteome

Publications

Transglutaminase 3 crosslinks the secreted gel-forming mucus component Mucin-2 and stabilizes the colonic mucus layer.

Similar Datasets

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