RT Journal Article
SR Electronic
T1 Dynamin-2 controls complement receptor 3- mediated phagocytosis completion and closure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.14.431164
DO 10.1101/2021.02.14.431164
A1 Anna Mularski
A1 Ryszard Wimmer
A1 Floriane Arbaretaz
A1 Gabriel Le Goff
A1 Florence Niedergang
YR 2021
UL http://biorxiv.org/content/early/2021/02/15/2021.02.14.431164.abstract
AB Phagocytosis is the mechanism of the internalization of large particles, microorganisms and cellular debris. The complement pathway represents one of the first mechanisms of defense against infection and the complement receptor 3 (CR3), which is highly expressed on macrophages, is a major receptor for many pathogens and debris. Key to dissecting the mechanisms by which CR3-mediated phagocytosis occurs, is understanding how the complex actin binding protein machinery and associated regulators interact with actin during phagocytosis, from triggering of receptor, through to phagosome formation and closure. However, how CR3-mediated phagosome completion and closure are orchestrated is not known. Here, we reveal that dynamin-2 is recruited concomitantly with polymerised actin at the site of the nascent phagosomes and accumulates until membrane scission. Inhibition of dynamin activity leads to stalled phagocytic cups and a decrease in the amount of F-actin at the site of phagocytosis. Acute inhibition of dynamin activity in living phagocytosing cells established that dynamin-2 plays a critical role in the effective scission of the CR3-phagosome from the plasma membrane. Thus, dynamin-2 has two distinct roles in CR3-mediated phagocytosis, in the assembly of the F-actin phagocytic cup and during phagosome scission.Competing Interest StatementThe authors have declared no competing interest.