Ezrin Promotes Actin Assembly at the Phagosome Membrane and Regulates Phago‐Lysosomal Fusion

Abstract

Phagosome maturation is defined as the process by which phagosomes fuse sequentially with endosomes and lysosomes to acquire an acidic pH and hydrolases that degrade ingested particles. While the essential role of actin cytoskeleton remodeling during particle internalization is well established, its role during the later stages of phagosome maturation remains largely unknown. We have previously shown that purified mature phagosomes assemble F-actin at their membrane, and that the ezrin-radixin-moesin (ERM) proteins ezrin and moesin participate in this process. Moreover, we provided evidence that actin assembly on purified phagosomes stimulates their fusion with late endocytic compartments in vitro. In this study, we further investigated the role of ezrin in phagosome maturation. We engineered a structurally open form of ezrin and demonstrated that ezrin binds directly to the actin assembly promoting factor N-WASP (Neural WiskottAldrich Syndrome Protein) by its FERM domain. Using a cell-free system, we found that ezrin stimulates F-actin assembly on purified phagosomes by recruiting the N-WASP-Arp2/3 machinery. Accordingly, we showed that the down-regulation of ezrin activity in macrophages by a dominant-negative approach caused reduced F-actin accumulation on maturing phagosomes. Furthermore, using fluorescence and electron microscopy, we found that ezrin is required for the efficient fusion between phagosomes and lysosomes. Live-cell imaging analysis supported the notion that ezrin is necessary for the fusogenic process itself, promoting the transfer of the lysosome content into the phagosomal lumen.

CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection

“…CASP4 facilitates cell migration by directly interacting with the actin interacting protein WDR1/AIP1, thereby allowing CFL1-dependent actin depolymerization in the context of chemotaxis [36]. During phagocytosis, F-actin assembly around phagosomes is crucial to guarantee efficient phagosome-lysosome fusion [60]. However, the role of CASP4-actin interaction in intracellular autophagosome trafficking is still unclear.…”

CD44 functions in Wnt signaling by regulating LRP6 localization and activation

“…It was shown that CD44 and Ezrin interact with N-WASP and promote the actin assembly via the N-WASP-Arp2/3 machinery. 30,49 Altogether, the role of CD44 both in the Wnt-independent LRP6 membrane targeting and in the Wnt-dependent LRP6 phosphorylation appear to be linked to the ability of CD44 to bind ERMs. Functions of ERMs that might explain their role in these two processes have been described.…”

Ezrin/Exocyst Complex Regulates Mucin 5AC Secretion Induced by Neutrophil Elastase in Human Airway Epithelial Cells

“…Ezrin is an important member of the ERM family. This protein specifically binds to actin and serves as a crosslinker between the plasma membrane and the cytoskeleton [28,29]. The Ezrin (NM-003379) gene is on chromosome 6q25.2-q26 and encodes 587 amino acids [30].…”