視黃醇（retinol）是維持機體的正常生長發(fā)育所必需的物質(zhì),，其代謝的產(chǎn)物通過與相關(guān)受體結(jié)合影響相關(guān)基因的轉(zhuǎn)錄而發(fā)揮作用,。人體所需的視黃醇大部分來源于飲食中的維生素A,，細胞以全視黃醇結(jié)合蛋白（holo-RBP4）循環(huán)形式攝入維生素A,，這是一種自我穩(wěn)定過程,，而這一過程明顯的依賴于多區(qū)域細胞膜蛋白STRA6,。有研究表明,，STRA6是維生素A進入細胞內(nèi)部的關(guān)鍵因素,。在人類中，STRA6的變異與Matthew-Wood綜合癥有關(guān),，這是一種遺傳性疾病,，其臨床表現(xiàn)主要為多個系統(tǒng)的發(fā)育畸形。
在2008年3月5日出版的《細胞—代謝》（Cell Metabolism）上，來自德國和美國的一組科學家表示,，他們發(fā)現(xiàn)了Matthew-Wood綜合癥的代謝基礎,。在研究中科學家們發(fā)現(xiàn)，在培養(yǎng)的NIH 3T3纖維原細胞中,，視黃醇從RBP4向細胞內(nèi)的轉(zhuǎn)移過程能夠被卵磷脂視黃醇?；D(zhuǎn)移酶（lecithin:retinol acyltransferase LRAT）大大增強，這一過程與STRA6相關(guān),。
視黃醇轉(zhuǎn)移是一個雙向過程,，這表明STRA6的作用很可能是視黃醇的輸送通道或是運輸因子。通過對斑馬魚胚胎的缺失功能分析,，研究人員發(fā)現(xiàn)STRA6的不足會造成發(fā)育中眼睛的維生素A缺失,。文章還表示，在缺乏STRA6的情況下,，holo-Rbp4會誘發(fā)多個胚胎組織中非特異性維生素A的過剩,，并損傷視黃酸受體信號以及基因調(diào)控。而STRA6缺乏所導致的致命結(jié)果,，例如顱面,、心臟缺陷以及眼部發(fā)育不良（microphthalmia）能通過降低胚胎中RBP4的濃度得到大大改觀，降低RBP4可通過嗎啉代低聚核苷酸（morpholino oligonucleotide）或者藥理學治療實現(xiàn),。（科學網(wǎng) 何宏輝/編譯）
生物谷推薦原始出處：
（Cell Metabolism）,，Vol 7, 258-268, 05 March 2008，Andrea Isken, Johannes von Lintig
RBP4 Disrupts Vitamin A Uptake Homeostasis in a STRA6-Deficient Animal Model for Matthew-Wood Syndrome
Andrea Isken,1 Marcin Golczak,2 Vitus Oberhauser,1 Silke Hunzelmann,1,2 Wolfgang Driever,1 Yoshikazu Imanishi,2 Krzysztof Palczewski,2, and Johannes von Lintig1,2,
1 Institut für Biologie 1, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany
2 Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4965, USA
Summary
The cellular uptake of vitamin A from its RBP4-bound circulating form (holo-RBP4) is a homeostatic process that evidently depends on the multidomain membrane protein STRA6. In humans, mutations in STRA6 are associated with Matthew-Wood syndrome, manifested by multisystem developmental malformations. Here we addressed the metabolic basis of this inherited disease. STRA6-dependent transfer of retinol from RBP4 into cultured NIH 3T3 fibroblasts was enhanced by lecithin:retinol acyltransferase (LRAT). The retinol transfer was bidirectional, strongly suggesting that STRA6 acts as a retinol channel/transporter. Loss-of-function analysis in zebrafish embryos revealed that Stra6 deficiency caused vitamin A deprivation of the developing eyes. We provide evidence that, in the absence of Stra6, holo-Rbp4 provokes nonspecific vitamin A excess in several embryonic tissues, impairing retinoic acid receptor signaling and gene regulation. These fatal consequences of Stra6 deficiency, including craniofacial and cardiac defects and microphthalmia, were largely alleviated by reducing embryonic Rbp4 levels by morpholino oligonucleotide or pharmacological treatments
