Back to Search
Start Over
A Diaphanous-related formin links Ras signaling directly to actin assembly in macropinocytosis and phagocytosis.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 Nov 22; Vol. 113 (47), pp. E7464-E7473. Date of Electronic Publication: 2016 Nov 07. - Publication Year :
- 2016
-
Abstract
- 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.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Actin-Related Protein 2-3 Complex metabolism
Dictyostelium metabolism
Microfilament Proteins genetics
Mutation
Phagocytosis
Pinocytosis
Proto-Oncogene Mas
Protozoan Proteins genetics
Protozoan Proteins metabolism
Signal Transduction
Actins metabolism
Dictyostelium physiology
Microfilament Proteins metabolism
ras Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 113
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 27821733
- Full Text :
- https://doi.org/10.1073/pnas.1611024113