Nature：科学家拍摄到Rab5蛋白激活过程图像

日本研究人员最近拍摄到一种名为“Rab5”的蛋白质的激活状态，这种蛋白质在白细胞吞噬死亡细胞时起控制作用。

日本京都大学的松田道行教授等研究人员在新一期英国《自然》（Nature）杂志网络版上报告说，“Rab5”控制白细胞吞噬、消化死亡细胞的进程。研究人员用基因技术对实验鼠进行了改造，一旦它的“Rab5”被激活，这种蛋白质的形状和颜色将会发生改变。

研究人员用了1个小时拍下约60张死亡细胞被吞噬过程的图像。连续播放这些图像，可以看到死亡细胞被吞噬后“Rab5”立刻变得非常活跃，这种活跃状态持续约10分钟。吞噬过程结束后，“Rab5”的活性一下降低，颜色也变回原样。

研究人员说，白细胞等的吞噬作用出现异常会导致免疫疾病，因此深入研究“Rab5”将有助于进一步了解这些疾病。（来源：新华网钱铮）

生物谷推荐原始出处：

（Nature），doi:10.1038/nature06857，Masahiro Kitano，Takeshi Nakamura

Imaging of Rab5 activity identifies essential regulators for phagosome maturation

Masahiro Kitano^1,³, Michio Nakaya^2,⁴, Takeshi Nakamura¹, Shigekazu Nagata^2,⁴ & 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. (Email: tnakamr@path1.med.kyoto-u.ac.jp).

Efficient phagocytosis of apoptotic cells is crucial for tissue homeostasis and the immune response^1,². 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.