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2016 ; 113
(47
): E7464-E7473
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A Diaphanous-related formin links Ras signaling directly to actin assembly in
macropinocytosis and phagocytosis
#MMPMID27821733
Junemann A
; Fili? V
; Winterhoff M
; Nordholz B
; Litschko C
; Schwellenbach H
; Stephan T
; Weber I
; Faix J
Proc Natl Acad Sci U S A
2016[Nov]; 113
(47
): E7464-E7473
PMID27821733
show ga
Phagocytosis and macropinocytosis are Ras-regulated and actin-driven processes
that depend on the dynamic rearrangements of the plasma membrane that protrudes
and internalizes extracellular material by cup-shaped structures. However, the
regulatory mechanisms underlying actin assembly in large-scale endocytosis remain
elusive. Here, we show that the Diaphanous-related formin G (ForG) from the
professional phagocyte Dictyostelium discoideum localizes to endocytic cups.
Biochemical analyses revealed that ForG is a rather weak nucleator but
efficiently elongates actin filaments in the presence of profilin. Notably,
genetic inactivation of ForG is associated with a strongly impaired endocytosis
and a markedly diminished F-actin content at the base of the cups. By contrast,
ablation of the Arp2/3 (actin-related protein-2/3) complex activator SCAR
(suppressor of cAMP receptor) diminishes F-actin mainly at the cup rim, being
consistent with its known localization. These data therefore suggest that ForG
acts as an actin polymerase of Arp2/3-nucleated filaments to allow for efficient
membrane expansion and engulfment of extracellular material. Finally, we show
that ForG is directly regulated in large-scale endocytosis by RasB and RasG,
which are highly related to the human proto-oncogene KRas.
|Actin-Related Protein 2-3 Complex/metabolism
[MESH]