Rip2 Is Required for Nod2-Mediated Lysozyme Sorting in Paneth Cells

Haifang Wang; Xinwen Zhang; Zhanguang Zuo; Qin Zhang; Ying Pan; Benhua Zeng; Wenxia Li; Hong Wei; Zhihua Liu

doi:10.4049/jimmunol.1601583

Rip2 Is Required for Nod2-Mediated Lysozyme Sorting in Paneth Cells

J Immunol. 2017 May 1;198(9):3729-3736. doi: 10.4049/jimmunol.1601583. Epub 2017 Mar 22.

Authors

Haifang Wang^{1

2}, Xinwen Zhang^{1

2}, Zhanguang Zuo^{1

2}, Qin Zhang¹, Ying Pan¹, Benhua Zeng³, Wenxia Li³, Hong Wei³, Zhihua Liu^{4

5}

Affiliations

¹ Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China; and.
⁴ Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; [email protected].
⁵ Center for Excellence in Biomacromolecules, Chinese Academy of Sciences, Beijing 100101, China.

PMID: 28330897
DOI: 10.4049/jimmunol.1601583

Abstract

Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2. Thus, we delineated a genetic pathway, consisting of Nod2-LRRK2-Rip2-Rab2a, which is required for lysozyme sorting. Taken together, our results indicate that the lysozyme-sorting process in Paneth cells is orchestrated by a number of host factors and highlight the importance of Paneth cell function in intestinal homeostasis.

MeSH terms

Animals
Cells, Cultured
Crohn Disease / metabolism*
Homeostasis
Humans
Intestines / pathology*
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Muramidase / metabolism*
NF-kappa B / metabolism
Nod2 Signaling Adaptor Protein / genetics
Nod2 Signaling Adaptor Protein / metabolism
Paneth Cells / metabolism*
Paneth Cells / pathology
Protein Transport
Receptor-Interacting Protein Serine-Threonine Kinase 2
Receptor-Interacting Protein Serine-Threonine Kinases / genetics
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
Secretory Vesicles / metabolism*
rab GTP-Binding Proteins / genetics
rab GTP-Binding Proteins / metabolism

Substances

NF-kappa B
Nod2 Signaling Adaptor Protein
Nod2 protein, mouse
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Lrrk2 protein, mouse
Receptor-Interacting Protein Serine-Threonine Kinase 2
Receptor-Interacting Protein Serine-Threonine Kinases
Ripk2 protein, mouse
Muramidase
Rab2a protein, mouse
rab GTP-Binding Proteins