近日科學家拍攝到Rab5蛋白激活過程圖像

【資料簡介】

日本研究人員zui近拍攝到一種名為“Rab5”的蛋白質的激活狀態，這種蛋白質在白細胞吞噬死亡細胞時起控制作用。
日本京都大學的松田道行教授等研究人員在新一期英國《自然》（Nature）雜志網絡版上報告說，“Rab5”控制白細胞吞噬、消化死亡細胞的進程。研究人員用基因技術對實驗鼠進行了改造，一旦它的“Rab5”被激活，這種蛋白質的形狀和顏色將會發生改變。
研究人員用了1個小時拍下約60張死亡細胞被吞噬過程的圖像。連續播放這些圖像，可以看到死亡細胞被吞噬后“Rab5”立刻變得非常活躍，這種活躍狀態持續約10分鐘。吞噬過程結束后，“Rab5”的活性一下降低，顏色也變回原樣。
研究人員說，白細胞等的吞噬作用出現異常會導致免疫疾病，因此深入研究“Rab5”將有助于進一步了解這些疾病。（來源：新華網 錢錚）
（Nature），doi:10.1038/nature06857，Masahiro Kitano，Takeshi Nakamura
Imaging of Rab5 activity identifies essential regulators for phagosome maturation
Masahiro Kitano1,3, Michio Nakaya2,4, Takeshi Nakamura1, Shigekazu Nagata2,4 & Michiyuki Matsuda1
Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, and,
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan
Solution Oriented Research for science and Technology, Japan Science and Technology Corporation, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Correspondence to: Takeshi Nakamura1 Correspondence and requests for materials should be addressed to T.N. (: tnakamr@path1.med.kyoto-u.ac.jp).
Efficient phagocytosis of apoptotic cells is crucial for tissue homeostasis and the immune response1, 2. Rab5 is known as a key regulator of the early endocytic pathway3 and we have recently shown that Rab5 is also implicated in apoptotic cell engulfment4; however, the precise spatio-temporal dynamics of Rab5 activity remain unknown. Here, using a newly developed fluorescence resonance energy transfer biosensor, we describe a change in Rab5 activity during the engulfment of apoptotic thymocytes. Rab5 activity on phagosome membranes began to increase on disassembly of the actin coat encapsulating phagosomes. Rab5 activation was either continuous or repetitive for up to 10 min, but it ended before the collapse of engulfed apoptotic cells. Expression of a dominant-negative mutant of Rab5 delayed this collapse of apoptotic thymocytes, showing a role for Rab5 in phagosome maturation. Disruption of microtubules with nocodazole inhibited Rab5 activation on the phagosome membrane without perturbing the engulfment of apoptotic cells. Furthermore, we found that Gapex-5 is the guanine nucleotide exchange factor essential for Rab5 activation during the engulfment of apoptotic cells. Gapex-5 was bound to a microtubule-tip-associating protein, EB1, whose depletion inhibited Rab5 activation during phagocytosis. We therefore propose a mechanistic model in which the recruitment of Gapex-5 to phagosomes through the microtubule network induces the transient Rab5 activation.