【摘 要】
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Vascular integrity is critical for normal physiological function of blood vessels and always broken-down in pathological conditions, such as hemorrhage.A mu
【机 构】
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StateKeyLaboratoryofBiomembraneandMembraneEngineering,Tsinghua-PekingCenterforLifeSciences,SchoolofL
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Vascular integrity is critical for normal physiological function of blood vessels and always broken-down in pathological conditions, such as hemorrhage.A mutant characterized by brain hemorrhage was found in an ENU mediated forward genetic screen.Further mapping uncovered that a point mutation ofX (T>G) was the cause of mutant phenotype, which was confirmed by rescue experiment and CRISPER/Cas9 mediated gene Knockout.This point mutation causes the substitution of a single amino acid of its protein product (L>R), changing the property of an amphiphilic a-helix.The mutant form was mislocated in cells, in turn affected its substrate Arf being recruited to Golgi apparatus;and this further inhibited membrane protein trafficking indicated by VSVG-GFP reporter assay.GST pull down assay suggested the L>R substitution decreased the interaction of X protein with Copa and Jup, which are component of COPI and adhesion junction, respectively.Our work suggests X may regulate vascular integrity through parallel ways.
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