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Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin
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نویسنده
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huang l. ,zhang y. ,xu c. ,gu x. ,niu l. ,wang j. ,sun x. ,bai x. ,xuan x. ,li q. ,shi c. ,yu b. ,miller h. ,yang g. ,westerberg l.s. ,liu w. ,song w. ,zhao x. ,liu c.
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منبع
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plos biology - 2017 - دوره : 15 - شماره : 8
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چکیده
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As the central hub of the metabolism machinery,the mammalian target of rapamycin complex 2 (mtorc2) has been well studied in lymphocytes. as an obligatory component of mtorc2,the role of rictor in t cells is well established. however,the role of rictor in b cells still remains elusive. rictor is involved in b cell development,especially the peripheral development. however,the role of rictor on b cell receptor (bcr) signaling as well as the underlying cellular and molecular mechanism is still unknown. this study used b cell–specfic rictor knockout (ko) mice to investigate how rictor regulates bcr signaling. we found that the key positive and negative bcr signaling molecules,phosphorylated brutons tyrosine kinase (pbtk) and phosphorylated sh2-containing inositol phosphatase (pship),are reduced and enhanced,respectively,in rictor ko b cells. this suggests that rictor positively regulates the early events of bcr signaling. we found that the cellular filamentous actin (f-actin) is drastically increased in rictor ko b cells after bcr stimulation through dysregulating the dephosphorylation of ezrin. the high actin-ezrin intensity area restricts the lateral movement of bcrs upon stimulation,consequently reducing bcr clustering and bcr signaling. the reduction in the initiation of bcr signaling caused by actin alteration is associated with a decreased humoral immune response in rictor ko mice. the inhibition of actin polymerization with latrunculin in rictor ko b cells rescues the defects of bcr signaling and b cell differentiation. overall,our study provides a new pathway linking cell metablism to bcr activation,in which rictor regulates bcr signaling via actin reorganization. © 2017 huang et al.
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آدرس
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chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, moe key laboratory of protein sciences,collaborative innovation center for diagnosis and treatment of infectious diseases,school of life sciences,institute for immunology,tsinghua university,beijing, China, moe key laboratory of protein sciences,collaborative innovation center for diagnosis and treatment of infectious diseases,school of life sciences,institute for immunology,tsinghua university,beijing, China, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, children’s hospital respiratory center of chongqing medical university,chongqing, China, department of pathogen biology,school of basic medicine,huazhong university of science and technology,wuhan, China, department of pathogen biology,school of basic medicine,huazhong university of science and technology,wuhan, China, department of intracellular pathogens,national institute of allergy and infectious diseases,hamilton,mt, United States, department of endocrinology,the second affiliated hospital,chongqing medical university,chongqing, China, department of microbiology tumor and cell biology,karolinska institutet,stockholm, Sweden, moe key laboratory of protein sciences,collaborative innovation center for diagnosis and treatment of infectious diseases,school of life sciences,institute for immunology,tsinghua university,beijing, China, department of cell biology and molecular genetics,university of maryland,college park,md, United States, chongqing key laboratory of child infection and immunity,children’s hospital of chongqing medical university,chongqing,china,department of pediatric research institute,children’s hospital of chongqing medical university,chongqing,china,ministry of education key laboratory of child development and disorders,children’s hospital of chongqing medical university,chongqing, China, department of pathogen biology,school of basic medicine,huazhong university of science and technology,wuhan, China
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Authors
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