CD 151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin
CD 151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin
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DOI：
10.1182/blood-2004-04-1512
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发表时间：
2004-10-15
期刊：
影响因子：
20.3
通讯作者：
Anstee, DJ
中科院分区：
文献类型：
--
作者：
Crew, VK;Burton, N;Anstee, DJ
Tetraspanins被认为有助于在细胞表面形成多蛋白复合体，但阐明这一作用的生物学重要性的证据很少。Tetraspanin CD151在肾脏与整合素α3β1和α6β1形成非常稳定的层粘连蛋白结合复合体，在皮肤与整合素α3β1和α6β4形成非常稳定的层粘连蛋白结合复合体。它是由染色体11p15.5上与MER2血型基因相同位置的基因编码的。我们发现CD151表达MER2血型抗原，定位于红细胞上。我们检测了3名MER2阴性的印度犹太血统的终末期肾病患者的CD151。除了遗传性肾炎，兄弟姐妹还有感觉神经性耳聋、胫前大疱性表皮松解症和轻微的β-地中海贫血。这3例患者是CD151外显子5的单核苷酸插入(G383)纯合子，导致140密码子的移码和过早停止信号。由此产生的截短蛋白将缺少其整合素结合域。我们认为，CD151对肾小球和肾小管基底膜的正确组装是必不可少的，在皮肤中具有重要的功能意义，可能是内耳的一种成分，并可能在红细胞生成中发挥作用。(C)2004年，由美国血液病学会提供。
Tetraspanins are thought to facilitate the formation of multiprotein complexes at cell surfaces, but evidence illuminating the biologic importance of this role is sparse. Tetraspanin CD151 forms very stable laminin-binding complexes with integrins alpha3beta1 and alpha6beta1 in kidney and alpha3beta1 and alpha6beta4 in skin. It is encoded by a gene at the same position on chromosome 11p15.5 as the MER2 blood group gene. We show that CD151 expresses the MER2 blood group antigen and is located on erythrocytes. We examined CD151 in 3 MER2-negative patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease. In addition to hereditary nephritis the sibs have sensorineural deafness, pretibial epidermolysis bullosa, and beta-thalassemia minor. The 3 patients are homozygous for a single nucleotide insertion (G383) in exon 5 of CD151, causing a frameshift and premature stop signal at codon 140. The resultant truncated protein would lack its integrin-binding domain. We conclude that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, has functional significance in the skin, is probably a component of the inner ear, and could play a role in erythropoiesis. (C) 2004 by The American Society of Hematology.