日本研究人员3月27日在《科学》杂志网络版上宣布，他们发现了嗜中性粒细胞向细菌等感染源移动的机制。这项成果将有助于提高免疫学研究和自体免疫疾病的治疗水平。
日本科学技术振兴机构和九州大学3月27日发表新闻公报说，研究人员此前曾发现，“DOCK2”蛋白质在嗜中性粒细胞向感染源移动过程中发挥重要作用，但却不知其具体机制。为此，研究人员利用绿色荧光蛋白与“DOCK2”蛋白融合，跟踪后者在嗜中性粒细胞内部的活动。结果发现，在两种磷脂质的作用下，“DOCK2”蛋白质聚集到嗜中性粒细胞内朝着感染源的一侧，使嗜中性粒细胞改变自身形态，更高效地向感染源移动。
嗜中性粒细胞是白细胞的一种，具有活跃的变形运动和吞噬功能，在机体防御机制中扮演着重要角色。（生物谷Bioon.com）
生物谷推荐原始出处：
Science March 26, 2009 DOI: 10.1126/science.1170179
Sequential Regulation of DOCK2 Dynamics by Two Phospholipids during Neutrophil Chemotaxis
Akihiko Nishikimi 1, Hideo Fukuhara 2, Wenjuan Su 3, Tsunaki Hongu 4, Shunsuke Takasuga 5, Hisashi Mihara 6, Qinhong Cao 7, Fumiyuki Sanematsu 2, Motomu Kanai 6, Hiroshi Hasegawa 4, Yoshihiko Tanaka 1, Masakatsu Shibasaki 6, Yasunori Kanaho 4, Takehiko Sasaki 5, Michael A. Frohman 3, Yoshinori Fukui 1*
1 Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.; Japan Science and Technology Agency, CREST, Tokyo 102-0075, Japan.
2 Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
3 Department of Pharmacology, Center for Developmental Genetics, Stony Brook University, NY 11794-5140, USA.
4 Graduate School of Comprehensive Human Sciences, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
5 Division of Microbiology, Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan.
6 Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
7 Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.; Present address: College of Biological Sciences, China Agricultural University, Beijing 100193, China.
* To whom correspondence should be addressed.
During chemotaxis activation of the small GTPase, Rac, is spatially regulated to organize the extension of membrane protrusions in the direction of migration. In neutrophils, Rac activation is primarily mediated by DOCK2, an atypical guanine nucleotide exchange factor. Upon stimulation, we found that DOCK2 rapidly translocated to the plasma membrane in a phosphatidylinositol 3,4,5-trisphosphate–dependent manner. However, subsequent accumulation of DOCK2 at the leading edge required phospholipase D–mediated synthesis of phosphatidic acid, which stabilized DOCK2 there via interaction with a polybasic amino acid cluster, resulting in increased local actin polymerization. When this interaction was blocked, neutrophils failed to form leading edges properly and exhibited defects in chemotaxis. Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis.
