Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis

Akihiko Nishikimi, Hideo Fukuhara, Wenjuan Su, Tsunaki Hongu, Shunsuke Takasuga, Hisashi Mihara, Qinhong Cao, Fumiyuki Sanematsu, Motomu Kanai, Hiroshi Hasegawa, Yoshihiko Tanaka, Masakatsu Shibasaki, Yasunori Kanaho, Takehiko Sasaki, Michael A. Frohman, Yoshinori Fukui

Research output: Contribution to journalArticle

187 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)384-387
Number of pages4
JournalScience
Volume324
Issue number5925
DOIs
Publication statusPublished - Apr 17 2009

Fingerprint

Chemotaxis
Phospholipids
Neutrophil Activation
Neutrophils
Guanine Nucleotide Exchange Factors
Phospholipase D
Phosphatidic Acids
Guanosine
Polymerization
Actins
Cell Membrane
Amino Acids
Membranes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Nishikimi, A., Fukuhara, H., Su, W., Hongu, T., Takasuga, S., Mihara, H., ... Fukui, Y. (2009). Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science, 324(5925), 384-387. https://doi.org/10.1126/science.1170179

Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. / Nishikimi, Akihiko; Fukuhara, Hideo; Su, Wenjuan; Hongu, Tsunaki; Takasuga, Shunsuke; Mihara, Hisashi; Cao, Qinhong; Sanematsu, Fumiyuki; Kanai, Motomu; Hasegawa, Hiroshi; Tanaka, Yoshihiko; Shibasaki, Masakatsu; Kanaho, Yasunori; Sasaki, Takehiko; Frohman, Michael A.; Fukui, Yoshinori.

In: Science, Vol. 324, No. 5925, 17.04.2009, p. 384-387.

Research output: Contribution to journalArticle

Nishikimi, A, Fukuhara, H, Su, W, Hongu, T, Takasuga, S, Mihara, H, Cao, Q, Sanematsu, F, Kanai, M, Hasegawa, H, Tanaka, Y, Shibasaki, M, Kanaho, Y, Sasaki, T, Frohman, MA & Fukui, Y 2009, 'Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis', Science, vol. 324, no. 5925, pp. 384-387. https://doi.org/10.1126/science.1170179
Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H et al. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. 2009 Apr 17;324(5925):384-387. https://doi.org/10.1126/science.1170179
Nishikimi, Akihiko ; Fukuhara, Hideo ; Su, Wenjuan ; Hongu, Tsunaki ; Takasuga, Shunsuke ; Mihara, Hisashi ; Cao, Qinhong ; Sanematsu, Fumiyuki ; Kanai, Motomu ; Hasegawa, Hiroshi ; Tanaka, Yoshihiko ; Shibasaki, Masakatsu ; Kanaho, Yasunori ; Sasaki, Takehiko ; Frohman, Michael A. ; Fukui, Yoshinori. / Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. In: Science. 2009 ; Vol. 324, No. 5925. pp. 384-387.
@article{1614e6791305440ba88ca3156e38d1e4,
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.",
author = "Akihiko Nishikimi and Hideo Fukuhara and Wenjuan Su and Tsunaki Hongu and Shunsuke Takasuga and Hisashi Mihara and Qinhong Cao and Fumiyuki Sanematsu and Motomu Kanai and Hiroshi Hasegawa and Yoshihiko Tanaka and Masakatsu Shibasaki and Yasunori Kanaho and Takehiko Sasaki and Frohman, {Michael A.} and Yoshinori Fukui",
year = "2009",
month = "4",
day = "17",
doi = "10.1126/science.1170179",
language = "English",
volume = "324",
pages = "384--387",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5925",

}

TY - JOUR

T1 - Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis

AU - Nishikimi, Akihiko

AU - Fukuhara, Hideo

AU - Su, Wenjuan

AU - Hongu, Tsunaki

AU - Takasuga, Shunsuke

AU - Mihara, Hisashi

AU - Cao, Qinhong

AU - Sanematsu, Fumiyuki

AU - Kanai, Motomu

AU - Hasegawa, Hiroshi

AU - Tanaka, Yoshihiko

AU - Shibasaki, Masakatsu

AU - Kanaho, Yasunori

AU - Sasaki, Takehiko

AU - Frohman, Michael A.

AU - Fukui, Yoshinori

PY - 2009/4/17

Y1 - 2009/4/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=65249117435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65249117435&partnerID=8YFLogxK

U2 - 10.1126/science.1170179

DO - 10.1126/science.1170179

M3 - Article

C2 - 19325080

AN - SCOPUS:65249117435

VL - 324

SP - 384

EP - 387

JO - Science

JF - Science

SN - 0036-8075

IS - 5925

ER -