title: Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis.
abstract: During chemotaxis, activation of the small guanosine triphosphatase 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 by means of 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.
authors.affiliation: Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nishikimi
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Su
authors.forename: Tsunaki
authors.initials: T
authors.lastname: Hongu
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takasuga
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mihara
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Cao
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Sanematsu
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui