Macropinosome maturation and fusion with tubular lysosomes in macrophages.

Racoosin, Esther L.; Swanson, Joel A.

doi:10.1083/jcb.121.5.1011

Cited by 309 publications

(297 citation statements)

References 39 publications

(39 reference statements)

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“…These contrasting results could be explained considering that the mechanisms that regulate endocytosis might differ in different cells. Supporting this possibility it has been described that, not only the routes for macropinocytosed Ags, but also the sensitivity of macropinocytosis to microtubule and microfilament destabilizing drugs differ between professional phagocytes and other cell types (38,59,(61)(62)(63). However, our observations made in bicarbonate-free medium support that, as observed in other cell types, acidification of cytosol exerts an inhibitory effect on DC endocytosis.…”

Section: Discussionsupporting

confidence: 89%

Acidosis Improves Uptake of Antigens and MHC Class I-Restricted Presentation by Dendritic Cells

Vermeulen

Giordano

Trevani

et al. 2004

The Journal of Immunology

111

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It is widely appreciated that inflammatory responses in peripheral tissues are usually associated to the development of acidic microenvironments. Despite this, there are few studies aimed to analyze the effect of extracellular pH on immune cell functions. We analyzed the impact of acidosis on the behavior of dendritic cells (DCs) derived from murine bone marrow. We found that extracellular acidosis (pH 6.5) markedly stimulated the uptake of FITC-OVA, FITC-dextran, and HRP by DCs. In fact, to reach similar levels of endocytosis, DCs cultured at pH 7.3 required concentrations of Ag in the extracellular medium almost 10-fold higher compared with DCs cultured at pH 6.5. Not only the endocytic capacity of DCs was up-regulated by extracellular acidosis, but also the expression of CD11c, MHC class II, CD40, and CD86 as well as the acquisition of extracellular Ags by DCs for MHC class I-restricted presentation. Importantly, DCs pulsed with Ag under acidosis showed an improved efficacy to induce both specific CD8+ CTLs and specific Ab responses in vivo. Our results suggest that extracellular acidosis improves the Ag-presenting capacity of DCs.

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Section: Discussionsupporting

confidence: 89%

Acidosis Improves Uptake of Antigens and MHC Class I-Restricted Presentation by Dendritic Cells

Vermeulen

Giordano

Trevani

et al. 2004

The Journal of Immunology

111

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“…We have observed that actinin-4 does indeed bind to filamentous actin and has bundling, but not nucleation, activity (Lotfi and Bean, unpublished observations). In macrophages, actinin-4 is transiently associated with macropinosomes before their fusion with lysosomes, as well as with phagosomes (Araki et al, 2000), suggesting a role for this molecule in two mechanistically similar types of endocytic trafficking (Racoosin and Swanson, 1993). Interestingly, the depletion of actinin-4 or disruption of hrs/actinin-4 interaction results in a decrease in Tf recycling with no effect on EGF recycling or degradation and no effect on internalization of either Tf or EGF.…”

Section: Discussionmentioning

confidence: 99%

CART: An Hrs/Actinin-4/BERP/Myosin V Protein Complex Required for Efficient Receptor Recycling

Yan

Wei

Kujala

et al. 2005

MBoC

114

121

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Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors. INTRODUCTIONEndocytosis is required for the uptake of essential nutrients from the extracellular environment as well as for retrieval of proteins and lipids that are added to the plasma membrane during fusion of regulated and constitutive secretory vesicles (De Camilli and Takei, 1996;Koenig and Ikeda, 1996;Robinson et al., 1996;Mukherjee et al., 1997;Schmid, 1997;Betz and Angleson, 1998;Koenig et al., 1998;Stoorvogel, 1998;D'Hondt et al., 2000;Gruenberg, 2001). The endocytic pathway can be separated into numerous stages based on the movement of cargo and the identification of morphologically defined compartments (De Camilli and Takei, 1996;Koenig and Ikeda, 1996;Robinson et al., 1996;Mukherjee et al., 1997;Schmid, 1997;Betz and Angleson, 1998;Koenig et al., 1998;Stoorvogel, 1998;D'Hondt et al., 2000;Gruenberg, 2001). Early events in the endocytic process include membrane invagination and vesicle budding from the plasma membrane, formation of transport vesicles, and fusion with early endosomes. Later events include cargo sorting, and additional transport/fusion steps, including those responsible for transport to the lysosome for degradation, and those responsible for recycling back to various compartments (De Camilli and Takei, 1996;Koenig and Ikeda, 1996;Robinson et al., 1996;Mukherjee et al., 1997;Schmid, 1997;Betz and Angleson, 1998;Koenig et al., 1998;Stoorvogel, 1998;D'Hondt et al., 2000;Gruenberg, 2001). Although much progress has been made in elucidating the molecular processes involved in early endocytic events, such as those involved in the genesis of clathrin-coated endocytic transport vesicles, an equally clear understanding of later events remains elusive.The early endosome is a crucial point in the endocytic pathway to sort cargo for transport to late endosomes for eventual degradation in the...

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“…Acquisition of sorting nexins (SNXs) promotes tubulation to facilitate cargo recycling and macropinosome maturation 21, 22, 23, 24, 25. As they move deeper into the cytoplasm, macropinosomes acidify and acquire Rab7, Rab21 and lysosome‐associated membrane protein 1 (LAMP1) 26, 27. While there is no consensus as to the final fate of macropinosomes, it has been shown that they can fuse with each other, LEs and LYs, a process that depends on the PI kinase, PIKfyve 26, 28, 29, 30.…”

mentioning

confidence: 99%

“…As they move deeper into the cytoplasm, macropinosomes acidify and acquire Rab7, Rab21 and lysosome‐associated membrane protein 1 (LAMP1) 26, 27. While there is no consensus as to the final fate of macropinosomes, it has been shown that they can fuse with each other, LEs and LYs, a process that depends on the PI kinase, PIKfyve 26, 28, 29, 30. Thus, the cargo is eventually degraded.…”

mentioning

confidence: 99%

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Rizopoulos

Balistreri

Kilcher

et al. 2015

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The prototypic poxvirus, vaccinia virus (VACV), occurs in two infectious forms, mature virions (MVs) and extracellular virions (EVs). Both enter HeLa cells by inducing macropinocytic uptake. Using confocal microscopy, live‐cell imaging, targeted RNAi screening and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing VACV MVs in HeLa cells. The vacuoles first acquired markers of early endosomes [Rab5, early endosome antigen 1 and phosphatidylinositol(3)P]. Prior to release of virus cores into the cytoplasm, they contained markers of late endosomes and lysosomes (Rab7a, lysosome‐associated membrane protein 1 and sorting nexin 3). RNAi screening of endocytic cell factors emphasized the importance of late compartments for VACV infection. Follow‐up perturbation analysis showed that infection required Rab7a and PIKfyve, confirming that VACV is a late‐penetrating virus dependent on macropinosome maturation. VACV EV infection was inhibited by depletion of many of the same factors, indicating that both infectious particle forms share the need for late vacuolar conditions for penetration.

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Macropinosome maturation and fusion with tubular lysosomes in macrophages.

Cited by 309 publications

References 39 publications

Acidosis Improves Uptake of Antigens and MHC Class I-Restricted Presentation by Dendritic Cells

Acidosis Improves Uptake of Antigens and MHC Class I-Restricted Presentation by Dendritic Cells

CART: An Hrs/Actinin-4/BERP/Myosin V Protein Complex Required for Efficient Receptor Recycling

Vaccinia Virus Infection Requires Maturation of Macropinosomes

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