Proc Natl Acad Sci U S A 2003,
PMID: 12743368
Le Clainche, Christophe; Pantaloni, Dominique; Carlier, Marie-France
Extension of lamellipodia, an important dissipative process in cell motility, is driven by the turnover of a polarized dendritic array of actin filaments. Motility is driven by catalytic cycles of filament attachment to Wiskott-Aldrich syndrome protein (WASP)-activated actin-related protein (Arp)2/3 complex at the leading edge, branch formation, and detachment, allowing subsequent growth of branched filaments. The morphology, mechanical strength, and lifetime of the array are determined by the processes of filament branching, debranching, and treadmilling. All three processes are controlled by ATP hydrolysis. ATP hydrolysis on F-actin is known to be at the origin of treadmilling. Here, by using radiolabeled ATP covalently bound to Arp2/3, we show that ATP is hydrolyzed on Arp2, not on Arp3, after a delay following filament branching. Hydrolysis of ATP on Arp2 promotes debranching of filaments and acts as a clock that controls the stability of dendritic actin arrays in lamellipodia. Finally, we propose that hydrolysis of ATP on G-actin in the ternary G-actin-WASP-Arp2/3 complex on branch formation destabilizes the WASP-actin interface and energetically facilitates the detachment step in the branching reaction.
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ARPC1A
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NCK1
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ACTG1
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BAIAP2
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ACTG1
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ACTB
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ARPC2
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NCKIPSD
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ACTR2
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ARPC2
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ACTR2
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ABI1
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ACTG1
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ACTG1
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ABI1
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NCKAP1
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ARPC5
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CDC42
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ACTG1
→
WIPF1
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ARPC1A
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ARPC5
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ARPC4
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ACTG1
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ARPC1A
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ACTG1
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ARPC2
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ARPC4
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ARPC4
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ACTR3
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ARPC3
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ACTR2
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ARPC5
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ACTR3
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ARPC4
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ARPC5
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ARPC4
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ACTB
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ARPC1A
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ACTB
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ARPC3
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ACTR2
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ARPC1A
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ACTR3
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ACTB
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ACTB
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ARPC2
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ARPC1A
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ARPC4
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ACTR3
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ARPC1A
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ACTG1
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ARPC1A
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ARPC3
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ARPC3
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(reaction)
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(reaction)
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ARPC3
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(reaction)
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(reaction)
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NCK1
(reaction)
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ACTR2
→
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(reaction)
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ACTR2
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ARPC5
→
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(reaction)
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(reaction)
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ARPC2
→
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(reaction)
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ARPC2
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(reaction)
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→
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(reaction)
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ARPC2
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→
BRK1
(reaction)
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ACTB
→
NCK1
(reaction)
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ARPC2
→
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(reaction)
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ACTB
→
NCKIPSD
(reaction)
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Reactome Reaction:
ARPC5
→
NCKAP1
(reaction)
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ACTG1
→
WIPF2
(reaction)
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ACTB
→
BRK1
(reaction)
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Reactome Reaction:
ARPC3
→
BRK1
(reaction)
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ARPC5
→
ABI1
(reaction)
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ARPC2
→
WASF2
(reaction)
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ACTB
→
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(reaction)
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ARPC1A
→
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(reaction)
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ARPC1A
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(reaction)
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ACTB
→
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(reaction)
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ARPC2
→
CDC42
(reaction)
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Reactome Reaction:
ACTG1
→
NCKIPSD
(reaction)
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Reactome Reaction:
ACTR3
→
BRK1
(reaction)
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Reactome Reaction:
ARPC5
→
CYFIP2
(reaction)
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ACTR3
→
GRB2
(reaction)
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Reactome Reaction:
ARPC5
→
BAIAP2
(reaction)
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ARPC5
→
GRB2
(reaction)
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Reactome Reaction:
ACTR3
→
NCK1
(reaction)
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ARPC3
→
WIPF2
(reaction)
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WASF2
→
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(reaction)
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ACTR3
→
WASL
(reaction)
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ACTG1
→
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(reaction)
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ARPC1A
→
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(reaction)
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ARPC5
→
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(reaction)
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Reactome Reaction:
ACTR2
→
WASL
(reaction)
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Reactome Reaction:
ARPC1A
→
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(reaction)
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ARPC3
→
BAIAP2
(reaction)
In total, 144 gene pairs are associated to this article in curated databases