NADPH Oxidase Is Internalized by Clathrin-coated Pits and Localizes to a Rab27A/B GTPase-regulated Secretory Compartment in Activated Macrophages

Ejlerskov, Patrick; Christensen, Dan Ploug; Beyaie, David; Burritt, James B.; Paclet, Marie-Hélène; Görlach, Agnes; Deurs, Bo van; Vilhardt, Frédérik

doi:10.1074/jbc.m111.293696

Cited by 35 publications

(39 citation statements)

References 59 publications

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“…This is in disagreement with results seen in DCs, in which Rab27a plays a role in phagosomal maturation, NADPH oxidase delivery to the phagosome, and antigen presentation [84]. In neutrophils or macrophages, participation of Rab27a in phagocytosis was only observed during engulfment of IgGopsonized red blood cells [82,85] but not IgG-opsonized zymosan, which not only engages Fc␥Rs but also binds and signals through mannose receptors and CR3 [85] or serum-opsonized live bacteria [36,82], suggesting that Rab27a is not essential for phagocytosis in neutrophils and macrophages under conditions of systemic infection that involve complex opsonization. Importantly, we demonstrated that different from Rab27a, Munc13-4 is essential for phagosomal maturation during engulfment of serum-opsonized bacteria in neutrophils [36].…”

Section: Regulation Of Neutrophil-specific Functions By Rab27a Gtpasecontrasting

confidence: 54%

Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors

Catz

2013

Journal of Leukocyte Biology

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Section: Regulation Of Neutrophil-specific Functions By Rab27a Gtpasecontrasting

confidence: 54%

Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors

Catz

2013

Journal of Leukocyte Biology

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“…Indeed, the Rab7 adaptor Mon1 is known to displace Rabex-5 from the phagosome, 58 and our results indicate that Rab17 sampling of the efferosome temporally overlaps with Rab7 recruitment to the efferosome. Another Rab GTPase, Rab27, can be localized to the phagosome, 59 activate Rab17 41 and drive exocytosis, 60, 61 indicating that it may be a candidate for the recruitment of Rab17 to the efferosome. However, we were unable to identify Rab27 on efferosomes in either our mass spectrometry screen or by immunofluorescence (data not shown), although the sensitivity and temporal limitations of these methods may have prevented identification of transient or weak Rab27 recruitment.…”

Section: Discussionmentioning

confidence: 99%

Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis

et al. 2016

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Macrophages engulf and destroy pathogens (phagocytosis) and apoptotic cells (efferocytosis), and can subsequently initiate adaptive immune responses by presenting antigens derived from engulfed materials. Both phagocytosis and efferocytosis share a common degradative pathway in which the target is engulfed into a membrane-bound vesicle, respectively, termed the phagosome and efferosome, where they are degraded by sequential fusion with endosomes and lysosomes. Despite this shared maturation pathway, macrophages are immunogenic following phagocytosis but not efferocytosis, indicating that differential processing or trafficking of antigens must occur. Mass spectrometry and immunofluorescence microscopy of efferosomes and phagosomes in macrophages demonstrated that efferosomes lacked the proteins required for antigen presentation and instead recruited the recycling regulator Rab17. As a result, degraded materials from efferosomes bypassed the MHC class II loading compartment via the recycling endosome – a process not observed in phagosomes. Combined, these results indicate that macrophages prevent presentation of apoptotic cell-derived antigens by preferentially trafficking efferocytosed, but not phagocytosed, materials away from the MHC class II loading compartment via the recycling endosome pathway.

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“…Bone resorption is a complex process combining secretion of protons by the vacuolar H+-ATPase and various lysosomal enzymes, and endocytosis/transcytosis of the degraded products via vesicle transport from apical to basolateral membrane29. Previous studies with various leukocytes have shown that Rab27A is involved in both exocytosis/secretion and endocytosis/phagocytosis303132. Rab27A-deficient neutrophils3334, eosinophils35, basophils36 all show impaired exocytosis.…”

Section: Discussionmentioning

confidence: 99%

Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome-Related Organelles in Osteoclasts

Shimada-Sugawara

Sakai

Okamoto

et al. 2015

Sci Rep

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Rab27A regulates transport of lysosome-related organelles (LROs) and release of secretory granules in various types of cells. Here, we identified up-regulation of Rab27A during differentiation of osteoclasts (OCLs) from bone-marrow macrophages (BMMs), by DNA microarray analysis. Rab27A deficiency in OCLs, using small interfering RNA (siRNA) knockdown in RAW-D cell line or BMMs derived from ashen mice, which display genetic defects in Rab27A expression, induced multinucleated and giant cells. Upon stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL), essential cytokines for OCL differentiation, phosphorylation levels of extracellular signal-regulated kinase (Erk), proto-oncogene tyrosine-protein kinase (Src), and p-38 were slightly enhanced in ashen BMMs than in wild-type BMMs. The cell surface level of c-fms, an M-CSF receptor, was slightly higher in ashen BMMs than in wild-type BMMs, and down-regulation of RANK, a RANKL receptor, was delayed. In addition to receptors, OCLs derived from ashen mice exhibited aberrant actin ring formation, abnormal subcellular localization of lysosome-associated membrane protein (LAMP2) and cathepsin K (CTSK), and marked reduction in resorbing activity. Thus, these findings suggest that Rab27A regulates normal transport of cell surface receptors modulating multinucleation and LROs in OCLs.

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NADPH Oxidase Is Internalized by Clathrin-coated Pits and Localizes to a Rab27A/B GTPase-regulated Secretory Compartment in Activated Macrophages

Cited by 35 publications

References 59 publications

Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors

Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors

Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis

Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome-Related Organelles in Osteoclasts

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