A role for SNX5 in the regulation of macropinocytosis

Lim, Jet Phey; Wang, Jack T. H.; Kerr, Markus C.; Teasdale, Rohan D.; Gleeson, Paul A.

doi:10.1186/1471-2121-9-58

Cited by 53 publications

(74 citation statements)

References 38 publications

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“…Some SNXs have also been reported to facilitate macropinosome maturation and function 23, 25, 59. Having identified SNX3 as a hit in the RNAi screen, we investigated its localization in cells that had internalized VACV MVs.…”

Section: Discussionmentioning

confidence: 99%

“…Macropinosomes may also acquire Rab34 and early endosome antigen 1 (EEA1) needed for pinosome formation and fusion 19, 20. 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.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Rizopoulos

Balistreri

Kilcher

et al. 2015

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“…An important class of phosphoinositide effectors which regulate a variety of endocytic trafficking events, including macropinocytosis, are the sorting nexins (SNXs) (Cullen, 2008). A number of SNXs have been implicated in the biogenesis of macropinosomes, including SNX1, SNX5, SNX9, SNX18 and SNX33 (Lim et al, 2008;Wang et al, 2010). Our earlier studies have shown that SNX5 in particular is required for the early events in the formation of macropinosomes at the cell surface not only in cultured cells (Lim et al, 2008) but also primary macrophages (Lim et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…A number of SNXs have been implicated in the biogenesis of macropinosomes, including SNX1, SNX5, SNX9, SNX18 and SNX33 (Lim et al, 2008;Wang et al, 2010). Our earlier studies have shown that SNX5 in particular is required for the early events in the formation of macropinosomes at the cell surface not only in cultured cells (Lim et al, 2008) but also primary macrophages (Lim et al, 2012). Following EGF stimulation of HEK293 cells, SNX5 is recruited to the plasma membrane and this recruitment is dependent on phosphatidylinositol (3,4)-bisphosphate (PIP 2 ) (Lim et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Sorting nexin 5 (SNX5) selectively regulates dorsal ruffle-mediated macropinocytosis in primary macrophages

Lim

Gosavi

Mintern

et al. 2015

Journal of Cell Science

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The regulation of macropinocytosis, a specialised endocytosis pathway, is important for immune cell function. However, it is not known whether the biogenesis of macropinosomes involves one or more distinct pathways. We previously identified sorting nexin 5 (SNX5) as a regulator of macropinocytosis in macrophages. Here, we show that bone-marrow-derived macrophages from SNX5-knockout mice had a 60-70% reduction in macropinocytic uptake of dextran or ovalbumin, whereas phagocytosis and retrograde transport from the plasma membrane to the Golgi was unaffected. In contrast, deficiency of SNX5 had no effect on macropinocytosis or antigen presentation by dendritic cells. Activation of macrophages with CSF-1 resulted in a localisation of SNX5 to actin-rich ruffles in a manner dependent on receptor tyrosine kinases. SNX5-deficient macrophages showed a dramatic reduction in ruffling on the dorsal surface following CSF-1 receptor activation, whereas peripheral ruffling and cell migration were unaffected. We demonstrate that SNX5 is acting upstream of actin polymerisation following CSF-1 receptor activation. Overall, our findings reveal the important contribution of dorsal ruffing to receptoractivated macropinocytosis in primary macrophages and show that SNX5 selectively regulates macropinosomes derived from the dorsal ruffles.

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“…Under normal conditions, macropinocytosis can also facilitate receptor-mediated signaling pathways, the entry of viral and bacterial pathogens, and cell motility (16) and is the mechanism by which macrophages and dendritic cells internalize antigens and cellular debris (16,17). More recently, macropinocytosis has also been shown to facilitate the uptake of amino acids in Ras-transformed pancreatic tumor cells to sustain their uncontrolled proliferation (14).…”

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confidence: 99%