+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Novel Role of TRPML2 in the Regulation of the Innate Immune Response

Novel Role of TRPML2 in the Regulation of the Innate Immune Response

Journal of Immunology 195(10): 4922-4932

TRPMLs (or mucolipins) constitute a family of endosomal cation channels with homology to the transient receptor potential superfamily. In mammals, the TRPML family includes three members: TRPML1-3. Although TRPML1 and TRPML3 have been well characterized, the cellular function of TRPML2 has remained elusive. To address TRPML2 function in a physiologically relevant cell type, we first analyzed TRPML2 expression in different mouse tissues and organs and found that it was predominantly expressed in lymphoid organs and kidney. Quantitative RT-PCR revealed tight regulation of TRPML2 at the transcriptional level. Although TRPML2 expression was negligible in resting macrophages, TRPML2 mRNA and protein levels dramatically increased in response to TLR activation both in vitro and in vivo. Conversely, TRPML1 and TRPML3 levels did not change upon TLR activation. Immunofluorescence analysis demonstrated that endogenous TRPML2 primarily localized to recycling endosomes both in culture and primary cells, in contrast with TRPML1 and TRPML3, which distribute to the late and early endosomal pathway, respectively. To better understand the in vivo function of TRPML2, we generated a TRPML2-knockout mouse. We found that the production of several chemokines, in particular CCL2, was severely reduced in TRPML2-knockout mice. Furthermore, TRPML2-knockout mice displayed impaired recruitment of peripheral macrophages in response to i.p. injections of LPS or live bacteria, suggesting a potential defect in the immune response. Overall, our study reveals interesting differences in the regulation and distribution of the members of the TRPML family and identifies a novel role for TRPML2 in the innate immune response.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 058430816

Download citation: RISBibTeXText

PMID: 26432893

DOI: 10.4049/jimmunol.1500163

Related references

Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells. Elife 7: -, 2018

The role of Toll-like receptors (TLR) in innate and adaptive immune responses and their function in immune response regulation. Postepy Higieny i Medycyny Doswiadczalnej 60: 52-63, 2006

Role of intracellular degradation system in regulation of innate immune response. Yakugaku Zasshi 134(11): 1157-1164, 2015

Role of miRNA-146a in the regulation of the innate immune response and cancer. Biochemical Society Transactions 36(Pt 6): 1211-1215, 2008

Differential role for CD80 and CD86 in the regulation of the innate immune response in murine polymicrobial sepsis. Plos One 4(8): E6600-E6600, 2010

Immune system development during early childhood in tropical Latin America: evidence for the age-dependent down regulation of the innate immune response. Clinical Immunology 138(3): 299-310, 2011

The innate immune response in the central nervous system and its role in glioma immune surveillance. Onkologie 27(5): 487-491, 2004

Regulation of innate immune response by MAP kinase phosphatase-1. Cellular Signalling 19(7): 1372-1382, 2007

Regulation of innate immune function in bovine oviduct epithelial cells in culture: the homeostatic role of epithelial cells in balancing Th1/Th2 response. Journal of Reproduction and Development 59(5): 470-478, 2014

Regulation of receptor-dependent activation of the innate immune response. Journal of Infectious Diseases 187 Suppl 2: S351-S355, 2003

Regulation of the innate immune response by fibronectin: synergism between the III-1 and EDA domains. Plos One 9(7): E102974-E102974, 2015

Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. Journal of Clinical Investigation 102(9): 1645-1652, 1998

Role of the HIN domain in regulation of innate immune responses. Molecular and Cellular Biology 34(1): 2-15, 2014

The Role of Ubiquitination in Regulation of Innate Immune Signaling. Current Issues in Molecular Biology 18: 1-10, 2015

Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response. Genes & Development 24(24): 2760-2765, 2011