Essential role of MFSD1-GLMP-GIMAP5 in lymphocyte survival and liver homeostasis.
Essential role of MFSD1-GLMP-GIMAP5 in lymphocyte survival and liver homeostasis.
复制标题
MFSD1-GLMP-GIMAP5 在淋巴细胞存活和肝脏稳态中的重要作用。
DOI：
10.1073/pnas.2314429120
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发表时间：
2023
影响因子：
11.1
通讯作者：
Choi,JinHuk
中科院分区：
文献类型：
--
作者：
Zhong,Xue;Moresco,JamesJ;Diedrich,JoleneK;Pinto,AntonioM;SoRelle,JeffreyA;Wang,Jianhui;Keller,Katie;Ludwig,Sara;Moresco,EvaMarieY;Beutler,Bruce;Choi,JinHuk
We detected ENU-induced alleles ofMfsd1(encoding the major facilitator superfamily domain containing 1 protein) that caused lymphopenia, splenomegaly, progressive liver pathology, and extramedullary hematopoiesis (EMH). MFSD1 is a lysosomal membrane-bound solute carrier protein with no previously described function in immunity. By proteomic analysis, we identified association between MFSD1 and both GLMP (glycosylated lysosomal membrane protein) and GIMAP5 (GTPase of immunity-associated protein 5). Germline knockout alleles ofMfsd1,Glmp, andGimap5each caused lymphopenia, liver pathology, EMH, and lipid deposition in the bone marrow and liver. We found that the interactions of MFSD1 and GLMP with GIMAP5 are essential to maintain normal GIMAP5 expression, which in turn is critical to support lymphocyte development and liver homeostasis that suppresses EMH. These findings identify the protein complex MFSD1-GLMP-GIMAP5 operating in hematopoietic and extrahematopoietic tissues to regulate immunity and liver homeostasis.
