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Moesin controls clathrin-mediated S1PR1 internalization in T cells
Akira Nomachi1, Masanori Yoshinaga2, Jaron Liu3
1Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Plos One
|December 21, 2013
Summary
Sphingosine 1-phosphate receptor 1 (S1PR1) internalization in T cells is crucial for lymphocyte trafficking. This study reveals moesin regulates S1PR1 internalization via clathrin-mediated endocytosis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Sphingosine 1-phosphate (S1P) is a lipid mediator regulating cellular functions, including immune cell trafficking.
- S1P receptor 1 (S1PR1) critically controls lymphocyte movement by mediating egress from and entry into lymphoid organs.
- The precise molecular mechanism of S1PR1 internalization in lymphocytes remains undefined.
Purpose of the Study:
- To elucidate the molecular mechanism of S1PR1 internalization in T cells.
- To investigate the role of moesin in S1PR1 internalization and lymphocyte trafficking.
Main Methods:
- Utilized T cells and moesin-deficient T cells.
- Employed pharmacological inhibition of clathrin.
- Administered FTY720 to moesin-deficient mice.
- Conducted ex vivo chemotaxis assays.
Main Results:
- Agonist-induced S1PR1 internalization in T cells occurs via clathrin-mediated endocytosis.
- S1PR1 relocalizes within clathrin-coated vesicles (CCVs) and early endosomes upon S1P stimulation.
- Moesin deficiency abrogates S1PR1 internalization and CCV formation in response to S1P.
- Moesin-deficient mice exhibit delayed lymphopenia and ex vivo S1P responsiveness after FTY720 treatment.
Conclusions:
- Moesin is a novel regulator of clathrin-dependent S1PR1 internalization.
- Moesin plays a critical role in S1PR1 internalization through CCV formation, impacting lymphocyte trafficking.
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