MOLECULAR-BASIS OF CD36 DEFICIENCY - EVIDENCE THAT A C-478-]T SUBSTITUTION (PROLINE90-]SERINE) IN CD36 CDNA ACCOUNTS FOR CD36 DEFICIENCY
MOLECULAR-BASIS OF CD36 DEFICIENCY - EVIDENCE THAT A C-478-]T SUBSTITUTION (PROLINE90-]SERINE) IN CD36 CDNA ACCOUNTS FOR CD36 DEFICIENCY
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DOI：
10.1172/jci117749
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发表时间：
1995-03-01
影响因子：
15.9
通讯作者：
MATSUZAWA, Y
中科院分区：
文献类型：
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作者：
KASHIWAGI, H;TOMIYAMA, Y;MATSUZAWA, Y
CD36缺乏症分为两个亚组：血小板和单核细胞均不表达CD36 （I型缺乏症），单核细胞尽管缺乏血小板CD36也表达CD36 （II型缺乏症）。我们已经证明血小板CD36 cDNA中的C-478- >T取代（脯氨酸90- >丝氨酸）在II型缺陷中占主导地位（Kashiwagi， H.， S. Honda， Y. Tomiyama， H. Mizutani， H. Take， Y. Honda， S. Kosugi， Y. Kanayama， Y. Kurata和Y. Matsuzawa. 1993）。Thromb。止血。69:481 - 484)。在本研究中，我们发现来自两个II型缺陷受试者的单核细胞CD36 cDNA杂合为C478和T478形式，而这些受试者的血小板CD36 cDNA仅由T478形式组成。在I型缺陷的受试者中，血小板和单核细胞CD36 cDNA仅显示T478形式。用C478或T478形式的CD36 cDNA转染细胞的表达实验显示，CD36存在81-kD的前体形式，并且81-kD前体形式向88-kD成熟形式的CD36的成熟明显受到取代的影响。突变的CD36前体随后在细胞质中降解。这些结果表明，C-478- >T取代通过翻译后修饰缺陷直接导致CD36缺乏症，这种取代是CD36缺乏症的主要缺陷。
CD36 deficiency is divided into two subgroups: neither platelets nor monocytes express CD36 (type I deficiency), and monocytes express CD36 in spite of the lack of platelet CD36 (type II deficiency). We have already demonstrated that a C-478-->T substitution (proline90-->serine) in platelet CD36 cDNA predominates in type II deficiency (Kashiwagi, H., S. Honda, Y. Tomiyama, H. Mizutani, H. Take, Y. Honda, S. Kosugi, Y. Kanayama, Y. Kurata, and Y. Matsuzawa. 1993. Thromb. Haemostasis. 69:481-484). In this study, we revealed that monocyte CD36 cDNA from two type II deficient subjects was heterozygous for C478 and T478 form, while platelet CD36 cDNA of these subjects consisted of only T478 form. In a type I deficient subject, both platelet and monocyte CD36 cDNA showed only T478 form. Expression assay using C478 or T478 form of CD36 cDNA transfected cells revealed that there was an 81-kD precursor form of CD36, and that the maturation of the 81-kD precursor form to the 88-kD mature form of CD36 was markedly impaired by the substitution. The mutated precursor form of CD36 was subsequently degraded in the cytoplasm. These results indicate that the C-478-->T substitution directly leads to CD36 deficiency via defects in posttranslational modification, and that this substitution is the major defects underlying CD36 deficiency.