Rip2 Is Required for Nod2-Mediated Lysozyme Sorting in Paneth Cells.
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.
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Haifang
H
Wang
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Xinwen
X
Zhang
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Zhanguang
0000-0002-3536-0618
Z
Zuo
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Qin
Q
Zhang
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Ying
Y
Pan
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China; and.
Benhua
0000-0002-8043-3900
B
Zeng
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China; and.
Wenxia
W
Li
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China; and.
Hong
H
Wei
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; zhihualiu@ibp.ac.cn.|Center for Excellence in Biomacromolecules, Chinese Academy of Sciences, Beijing 100101, China.
Zhihua
0000-0002-0269-0901
Z
Liu
D000818:Animals; D002478:Cells, Cultured; D003424:Crohn Disease / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007422:Intestines / Q000473:pathology*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009113:Muramidase / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020693:rab2 GTP-Binding Protein
D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009113:Muramidase; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020691:rab GTP-Binding Proteins; C495945:Nod2 protein, mouse; C495279:Lrrk2 protein, mouse; C506255:Ripk2 protein, mouse; C000602046:Rab2a protein, mouse; D020693:rab2 GTP-Binding Protein