The non-classical export routes: FGF1 and IL-1α point the way

Prudovsky, Igor; Mandinova, Anna; Soldi, Raffaella; Bagalá, Cinzia; Graziani, Irene; Landriscina, Matteo; Tarantini, Francesca; Duarte, Maria F.; Bellum, Stephen; Doherty, Holly; Maciag, Thomas

doi:10.1242/jcs.00872

Cited by 183 publications

(200 citation statements)

References 124 publications

(149 reference statements)

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“…When cultured cells were deprived of serum, both ProTa and S100A13 were completely lost from cells at the time point of 3 h. The cellular loss of S100A13 and ProTa was also blocked by amlexanox, a potent inhibitor of S100A13. [8][9][10][11]18 Quantitative immunoblot analysis confirmed that amlexanox abolished the serum-deprivation stressinduced extracellular release of ProTa (Figure 3c). …”

Section: Resultsmentioning

confidence: 65%

“…This re-distribution was completely reversed by co-injection of ATP (Figure 2c, upper right 4 panels). On the other hand, serum deprivation caused a re-distribution of ProTa from nucleus to cytosol, but did not result in extracellular release in the presence of amlexanox, which inhibits the release of proteins lacking a signal peptide sequence [8][9][10][11] (Figure 2c, lower panels). Similarly, co-injection of ATP reversed the nucleusto-cytosol export.…”

Section: Resultsmentioning

confidence: 99%

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Stress-induced non-vesicular release of prothymosin-α initiated by an interaction with S100A13, and its blockade by caspase-3 cleavage

Matsunaga

Ueda

2010

Cell Death Differ

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The nuclear protein prothymosin-a (ProTa), which lacks a signal peptide sequence, is released from neurons and astrocytes on ischemic stress and exerts a unique form of neuroprotection through an anti-necrotic mechanism. Ischemic stress-induced ProTa release is initiated by a nuclear release, followed by extracellular release in a non-vesicular manner, in C6 glioma cells. These processes are caused by ATP loss and elevated Ca 2 þ , respectively. S100A13, a Ca 2 þ -binding protein, was identified to be a major protein co-released with ProTa in an immunoprecipitation assay. The Ca 2 þ -dependent interaction between ProTa and S100A13 was found to require the C-terminal peptide sequences of both proteins. In C6 glioma cells expressing a D88-98 mutant of S100A13, serum deprivation caused the release of S100A13 mutant, but not of ProTa. When cells were administered apoptogenic compounds, ProTa was cleaved by caspase-3 to generate a C-terminal peptide-deficient fragment, which lacks the nuclear localization signal (NLS). However, there was no extracellular release of ProTa. All these results suggest that necrosisinducing stress induces an extacellular release of ProTa in a non-vesicular manner, whereas apoptosis-inducing stress does not, owing to the loss of its interaction with S100A13, a cargo molecule for extracellular release.

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Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Stress-induced non-vesicular release of prothymosin-α initiated by an interaction with S100A13, and its blockade by caspase-3 cleavage

Matsunaga

Ueda

2010

Cell Death Differ

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“…Since we previously demonstrated that when the components of the FGF1 release complex are co-expressed, they localize at the plasma membrane in response to stress [16], the observation that FGF1 release complex members destabilize acidic pL liposomes suggests a critical role for plasma membrane pL in the assembly and export of the FGF1 release complex [12]. Particularly, the preference exhibited by p40 Syt1 in permeabilizing pI liposomes indicates the existence of sites of specific pL compositions that recruit different constituents of the FGF1 release complex at the inner leaflet of the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to another ubiquitous and biologically important prototype member of the FGF family, FGF2, FGF1 belongs to a large group of proteins that lack a conventional signal sequence and gain access to the extracellular compartment independently of the endoplasmic reticulum (ER)-Golgi apparatus [4][5][6][7][8][9][10][11][12][13]. Indeed, FGF1 release is insensitive to Brefeldin A [14], which blocks ER-to-Golgi vesicular transport [15], and FGF1 does not appear to be present in the cytoplasmic vesicles [16].…”

Section: Introductionmentioning

confidence: 99%

Release of FGF1 and p40 synaptotagmin 1 correlates with their membrane destabilizing ability

Graziani

Bagalá

Duarte

et al. 2006

Biochemical and Biophysical Research Communications

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Fibroblast growth factor (FGF)1 is released from cells as a constituent of a complex that contains the small calcium binding protein S100A13, and the p40 kDa form of synaptotagmin (Syt)1, through an ER-Golgi-independent stress-induced pathway. FGF1 and the other components of its secretory complex are signal peptide-less proteins. We examined their capability to interact with lipid bilayers by studying protein-induced carboxyfluorescein release from liposomes of different phospholipid (pL) compositions. FGF1, p40 Syt1, and S100A13 induced destabilization of liposomes composed of acidic but not of zwitterionic pL. We produced mutants of FGF1 and p40 Syt1, in which specific basic amino acid residues in the regions that bind acidic pL were substituted. The ability of these mutants to induce liposomes destabilization was strongly attenuated, and they exhibited drastically diminished spontaneous and stress-induced release. Apparently, the non-classical release of FGF1 and p40 Syt1 involves destabilization of membranes containing acidic pL.

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“…Both FGF1 and FGF2 have previously been impli- cated in metanephric development (Perantoni et al, 1995;Barasch et al, 1997;Qiao et al, 2001;Zhao et al, 2004). While the FGFs are secreted via a mechanism distinct from the use of an ER signal peptide (Prudovsky et al, 2003) and hence would not have been included in the soluble/secreted class using our prediction tools, these transcripts were actually not outliers themselves, highlighting the need for parallel analyses of signalling pathways.…”

Section: Ingenuity Pathway Analysismentioning

confidence: 97%

Definition and spatial annotation of the dynamic secretome during early kidney development

et al. 2006

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The term "secretome" has been defined as a set of secreted proteins (Grimmond et al.[2003] Genome Res 13:1350 -1359). The term "secreted protein" encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants.

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The non-classical export routes: FGF1 and IL-1α point the way

Cited by 183 publications

References 124 publications

Stress-induced non-vesicular release of prothymosin-α initiated by an interaction with S100A13, and its blockade by caspase-3 cleavage

Stress-induced non-vesicular release of prothymosin-α initiated by an interaction with S100A13, and its blockade by caspase-3 cleavage

Release of FGF1 and p40 synaptotagmin 1 correlates with their membrane destabilizing ability

Definition and spatial annotation of the dynamic secretome during early kidney development

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