Naslov
A Diaphanous-related formin links Ras signaling directly to actin assembly in macropinocytosis and phagocytosis

Autori
Junemann, A. ; Filić, Vedrana ; Winterhoff, M. ; Nordholz, B. ; Litschko, C. ; Schwellenbach, H. ; Stephan, T. ; Weber, Igor ; Faix, J.

Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 113 (2016), 47; E7464-E7473

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Arp2/3 complex; formin; macropinocytosis; phagocytosis; Ras

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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