Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been...Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been devoted to the identification of SARS-CoV-2 infection-dependent host factors.CRISPR-based activation(Konermann et al.,2015).展开更多
Candida albicans deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence.However,the intricate interactions between the fungus and the host remain poorly understood,and a...Candida albicans deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence.However,the intricate interactions between the fungus and the host remain poorly understood,and a comprehensive inventory of fungal virulence factors has yet to be established.In this study,we identified a C.albicans secretory effector protein Sce1,whose induction and secretion are associated with vagina‐simulative conditions and chlamydospore formation.Sequence alignment showed that Sce1 belongs to a Pir family in C.albicans,which is conserved across several fungi and primarily characterized as aβ‐glucan binding protein in the Saccharomyces cerevisiae.Mechanically,Sce1 is primarily localized to the cell wall in a cleaved form as an alkali‐labileβ‐1,3‐glucan binding protein and plays a role in maskingβ‐glucan in acidic environments and chlamydospores,a feature that might underline C.albicans'ability to evade host immunity.Further,a cleaved short form of Sce1 protein could be released into extracellular compartments and presented in bone marrow‐derived macrophages infected with chlamydospores.This cleaved short form of Sce1 also demonstrated a unique ability to trigger the caspases‐8/9‐dependent apoptosis in various host cells.Correspondingly,genetic deletion of SCE1 led to dampened vaginal colonization of C.albicans and diminished fungal virulence during systemic infection.The discovery of Sce1 as a versatile virulence effector that executes at various compartments sheds light on the fungus–host interactions and C.albicans pathogenesis.展开更多
Spleen tyrosine kinase(SYK)is a non-receptor tyrosine kinase,which plays an essential role in both innate and adaptive immunity.However,the key molecular mechanisms that regulate SYK activity are poorly understood.Her...Spleen tyrosine kinase(SYK)is a non-receptor tyrosine kinase,which plays an essential role in both innate and adaptive immunity.However,the key molecular mechanisms that regulate SYK activity are poorly understood.Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation.We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK.This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors(CLRs).展开更多
文摘Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been devoted to the identification of SARS-CoV-2 infection-dependent host factors.CRISPR-based activation(Konermann et al.,2015).
基金supported by the National Natural Science Foundation of China grants(31970144,81720108019,and 32030040)the National Key Research and Development Program of China(2021YFA1301400)the Shanghai Municipal Science and Technology Major Project(2019SHZDZX02).
文摘Candida albicans deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence.However,the intricate interactions between the fungus and the host remain poorly understood,and a comprehensive inventory of fungal virulence factors has yet to be established.In this study,we identified a C.albicans secretory effector protein Sce1,whose induction and secretion are associated with vagina‐simulative conditions and chlamydospore formation.Sequence alignment showed that Sce1 belongs to a Pir family in C.albicans,which is conserved across several fungi and primarily characterized as aβ‐glucan binding protein in the Saccharomyces cerevisiae.Mechanically,Sce1 is primarily localized to the cell wall in a cleaved form as an alkali‐labileβ‐1,3‐glucan binding protein and plays a role in maskingβ‐glucan in acidic environments and chlamydospores,a feature that might underline C.albicans'ability to evade host immunity.Further,a cleaved short form of Sce1 protein could be released into extracellular compartments and presented in bone marrow‐derived macrophages infected with chlamydospores.This cleaved short form of Sce1 also demonstrated a unique ability to trigger the caspases‐8/9‐dependent apoptosis in various host cells.Correspondingly,genetic deletion of SCE1 led to dampened vaginal colonization of C.albicans and diminished fungal virulence during systemic infection.The discovery of Sce1 as a versatile virulence effector that executes at various compartments sheds light on the fungus–host interactions and C.albicans pathogenesis.
基金This work was supported by grants from the National Natural Science Foundation of China(81930039,31730026,81525012)the Key Research and Development Projects of Shandong Province(2019GSF108133).
文摘Spleen tyrosine kinase(SYK)is a non-receptor tyrosine kinase,which plays an essential role in both innate and adaptive immunity.However,the key molecular mechanisms that regulate SYK activity are poorly understood.Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation.We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK.This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors(CLRs).
