在細(xì)胞中,,不同的基因都處于沉默狀態(tài)(中間和底部),,相比正常細(xì)胞(最上面),,特殊位點的分泌過程開始進(jìn)行(綠色代表開始分泌) (Credit: Image courtesy of UCD Conway Institute of Biomolecular & Biomedical Research)
近日,,愛爾蘭都柏林大學(xué)和歐洲分子生物學(xué)實驗室(EMBL)的研究者共同努力,揭示了人類基因組所編碼的15%的蛋白質(zhì)用于細(xì)胞來進(jìn)行分泌的過程,,這項研究使得我們評定超過800萬個單獨細(xì)胞的功能成為可能,。研究者Jeremy Simpson表示,這是首次對人類細(xì)胞分泌過程的一個全基因組的評估,。相關(guān)研究成果刊登在了近日的國際雜志Nature Cell Biology上,。
分泌過程對于機(jī)體任何類型的細(xì)胞都是一個基礎(chǔ)的過程,分泌過程可以使機(jī)體將激素類運輸?shù)窖苤?,將消化酶運輸?shù)侥c道,,以及在細(xì)胞間運輸各種信號分子等。然而,,時至今日,,由于技術(shù)限制,并不允許科學(xué)家縱覽細(xì)胞所進(jìn)行的生產(chǎn)蛋白質(zhì),、脂質(zhì),,包裝以及運輸?shù)冗^程。
以前關(guān)于分泌過程的研究只是基于在基因的小分子簇上或者在過于簡單的生物體中(如果蠅),,當(dāng)然所識別的蛋白質(zhì)和人類的并不一樣,;如今,研究者使用高內(nèi)涵篩選的方法,,可以系統(tǒng)性地以人類22000個基因為靶點,,并且追尋其特殊的路徑,研究者在超過800萬個自爆中用熒光標(biāo)記蛋白質(zhì),,然后追蹤其經(jīng)過的路徑,。
研究者分析了70萬張顯微成像圖片,發(fā)現(xiàn)了554個影響分泌的蛋白質(zhì)以及發(fā)現(xiàn)了143個影響細(xì)胞早期分泌或者影響高爾基體形態(tài)的蛋白質(zhì),。膜運輸途徑聯(lián)系著細(xì)胞膜和細(xì)胞器之間的溝通關(guān)系,,確保細(xì)胞可以維持其蛋白質(zhì)以及脂質(zhì)的補(bǔ)充,最終維持細(xì)胞的正常功能,。細(xì)胞的分泌系統(tǒng)有能力處理一系列的貨物分子,,并且可以利用密集型的調(diào)節(jié)機(jī)器。這項研究重點研究了細(xì)胞質(zhì)外殼蛋白復(fù)合物早期特殊的調(diào)節(jié)元件,。相關(guān)研究由愛爾蘭科學(xué)基金會支持,。(生物谷Bioon.com)
編譯自:First Genome-Wide Assessment of Secretion in Human Cells
編譯者:T.Shen
doi:10.1038/ncb2510
PMC:
PMID:
Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway
Jeremy C. Simpson,1 Brigitte Joggerst,2 Vibor Laketa,2 Fatima Verissimo,2 Cihan Cetin,2 Holger Erfle,2, 6 Mariana G. Bexiga,1 Vasanth R. Singan,1 Jean-Karim Hériché,3 Beate Neumann,3 Alvaro Mateos,2 Jonathon Blake,4 Stephanie Bechtel,5 Vladimir Benes,4 Stefan Wiemann,5 Jan Ellenberg2, 3 & Rainer Pepperkok2
The secretory pathway in mammalian cells has evolved to facilitate the transfer of cargo molecules to internal and cell surface membranes. Use of automated microscopy-based genome-wide RNA interference screens in cultured human cells allowed us to identify 554 proteins influencing secretion. Cloning, fluorescent-tagging and subcellular localization analysis of 179 of these proteins revealed that more than two-thirds localize to either the cytoplasm or membranes of the secretory and endocytic pathways. The depletion of 143 of them resulted in perturbations in the organization of the COPII and/or COPI vesicular coat complexes of the early secretory pathway, or the morphology of the Golgi complex. Network analyses revealed a so far unappreciated link between early secretory pathway function, small GTP-binding protein regulation, actin cytoskeleton organization and EGF-receptor-mediated signalling. This work provides an important resource for an integrative understanding of global cellular organization and regulation of the secretory pathway in mammalian cells.