Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma membrane following EGF stimulation

Merino-Trigo, Ana; Kerr, Markus C.; Houghton, Fiona; Lindberg, Anna; Mitchell, Christina A.; Teasdale, Rohan D.; Gleeson, Paul A.

doi:10.1242/jcs.01561

Cited by 63 publications

(89 citation statements)

References 55 publications

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“…Previously we reported the change in membrane recruitment of SNX5 following stimulation of cells with EGF using immunofluorescence on fixed cell monolayers (Merino-Trigo et al, 2004). Following EGF treatment SNX5 was recruited to actin-rich regions of the plasma membrane and to large endosomal structures at the cell periphery.…”

Section: Snx5 Associates With Highly Dynamic Tubular Extensions Of Thmentioning

confidence: 89%

“…Recently, we reported that unlike SNX1, which, depending on the assay used, binds PtdIns(3)P, PtdIns(3,5)P 2 (Cozier et al, 2002) or PtdIns(3,4,5)P 3 (Cozier et al, 2002;Zhong et al, 2002), SNX5 has the capacity to directly bind PtdIns(3)P and PtdIns(3,4)P 2 (Merino-Trigo et al, 2004). We also reported that SNX5 is transiently recruited to actin-rich regions of the plasma membrane in response to stimulation of the cell with epidermal growth factor (EGF) (Merino-Trigo et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…We also reported that SNX5 is transiently recruited to actin-rich regions of the plasma membrane in response to stimulation of the cell with epidermal growth factor (EGF) (Merino-Trigo et al, 2004). We speculated that given this shift in the subcellular distribution of SNX5 in response to EGF and the association of SNX5 with enlarged endosomal structures (Merino-Trigo et al, 2004), SNX5 might play a role in macropinocytosis.…”

Section: Introductionmentioning

confidence: 99%

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Visualisation of macropinosome maturation by the recruitment of sorting nexins

Kerr

Lindsay

Luetterforst

et al. 2006

Journal of Cell Science

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129

162

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We report that phosphoinositol-binding sorting nexin 5 (SNX5) associates with newly formed macropinosomes induced by EGF stimulation. We used the recruitment of GFP-SNX5 to macropinosomes to track their maturation. Initially, GFP-SNX5 is sequestered to discrete subdomains of the macropinosome; these subdomains are subsequently incorporated into highly dynamic, often branched, tubular structures. Time-lapse videomicroscopy revealed the highly dynamic extension of SNX5-labelled tubules and their departure from the macropinosome body to follow predefined paths towards the perinuclear region of the cell, before fusing with early endosomal acceptor membranes. The extension and departure of these tubular structures occurs rapidly over 5-10 minutes and is dependent upon intact microtubules. As the tubular structures depart from the macropinosome there is a reduction in the surface area and an increase in tension of the limiting membrane of the macropinosome. In addition to the recruitment of SNX5 to the macropinosome, Rab5, SNX1 and EEA1 are also recruited by newly formed macropinosomes, followed by the accumulation of Rab7. SNX5 forms heterodimers with SNX1 and this interaction is required for endosome association of SNX5. We propose that the departure of SNX5-positive tubules represents a rapid mechanism of recycling components from macropinosomes thereby promoting their maturation into Rab7-positive structures. Collectively these findings provide a detailed real-time characterisation of the maturation process of the macropinocytic endosome.

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Section: Snx5 Associates With Highly Dynamic Tubular Extensions Of Thmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Visualisation of macropinosome maturation by the recruitment of sorting nexins

Kerr

Lindsay

Luetterforst

et al. 2006

Journal of Cell Science

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129

162

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“…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%

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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“…Our previous work has shown that SNX5 binds both phosphatidylinositol 3-phosphate (PI3P) and PIP 2 , the latter of which is derived from cell signalling events (Merino-Trigo et al, 2004) and that SNX5 is localised to newly emerging macropinosomes following receptor activation in HEK293 cells (Lim et al, 2008;Merino-Trigo et al, 2004). In this paper, we show that SNX5 is located at the plasma membrane following receptor activation of macrophages and that the plasma membrane localization of SNX5 is dependent on kinase activity of the CSF-1 receptor.…”

Section: Discussionmentioning

confidence: 62%

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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Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma membrane following EGF stimulation

Cited by 63 publications

References 55 publications

Visualisation of macropinosome maturation by the recruitment of sorting nexins

Visualisation of macropinosome maturation by the recruitment of sorting nexins

Vaccinia Virus Infection Requires Maturation of Macropinosomes

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

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