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Secretion of novel SEL1L endogenous variants is promoted by ER stress/UPR via endosomes and shed vesicles in human cancer cells.

Cattaneo M, Lotti LV, Martino S, Alessio M, Conti A, Bachi A, Mariani-Costantini R, Biunno I - PLoS ONE (2011)

Bottom Line: We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28.Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA.P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biomedical Technologies, National Research Council, Milan, Italy.

ABSTRACT
We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28. Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA. P38 is expressed and constitutively secreted, with increase after ER stress, in the KMS11 myeloma line and in the breast cancer lines MCF7 and SKBr3, but not in the non-tumorigenic breast epithelial MCF10A line. P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress. Consistently with the presence of p38 and p28 in culture media, morphological studies of SKBr3 and KMS11 cells detect N-terminal SEL1L immunolabeling in secretory/degradative compartments and extracellularly-released membrane vesicles. Our findings suggest that the two new SEL1L variants are engaged in endosomal trafficking and secretion via vesicles, which could contribute to relieve ER stress in tumorigenic cells. P38 and p28 could therefore be relevant as diagnostic markers and/or therapeutic targets in cancer.

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Related in: MedlinePlus

Localizations of SEL1L in MG132-treated KMS11 cells.Cryoimmunogold electron microscopy of MG132-treated cells labeled with 15 nm gold for SEL1L N-terminus shows SEL1L localized mainly in internal vesicles of multivesicular bodies (arrows); with additional labeling in the endoplasmic reticulum, Golgi complex and intracellular vesicles (panels A, C, arrows). In panel B a small SEL1L-labeled multivesicular body (arrow) lies in direct apposition to the plasma membrane. Exosomal-like vesicles, that seem to originate from fusion of this multivesicular body with the plasma membrane, bud into the extracellular space (arrowhead), suggesting that SEL1L is secreted via exosomes derived from the multivesicular body. Bars: 0.1 µm; er: endoplasmic reticulum; G: Golgi apparatus; MVB: multivesicular body; PM: plasma membrane.
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pone-0017206-g005: Localizations of SEL1L in MG132-treated KMS11 cells.Cryoimmunogold electron microscopy of MG132-treated cells labeled with 15 nm gold for SEL1L N-terminus shows SEL1L localized mainly in internal vesicles of multivesicular bodies (arrows); with additional labeling in the endoplasmic reticulum, Golgi complex and intracellular vesicles (panels A, C, arrows). In panel B a small SEL1L-labeled multivesicular body (arrow) lies in direct apposition to the plasma membrane. Exosomal-like vesicles, that seem to originate from fusion of this multivesicular body with the plasma membrane, bud into the extracellular space (arrowhead), suggesting that SEL1L is secreted via exosomes derived from the multivesicular body. Bars: 0.1 µm; er: endoplasmic reticulum; G: Golgi apparatus; MVB: multivesicular body; PM: plasma membrane.

Mentions: Correspondingly, in MG132-treated KMS11 cells, IEM showed that SEL1L was present in vesicles dispersed in the peripheral cytoplasm or associated with late endosomes/MVBs (Figure 5A, C). Furthermore, in areas where MVBs were adjacent to the PM, SEL1L-labeled vesicles appeared to emerge into the extracellular space (Figure 5B).


Secretion of novel SEL1L endogenous variants is promoted by ER stress/UPR via endosomes and shed vesicles in human cancer cells.

Cattaneo M, Lotti LV, Martino S, Alessio M, Conti A, Bachi A, Mariani-Costantini R, Biunno I - PLoS ONE (2011)

Localizations of SEL1L in MG132-treated KMS11 cells.Cryoimmunogold electron microscopy of MG132-treated cells labeled with 15 nm gold for SEL1L N-terminus shows SEL1L localized mainly in internal vesicles of multivesicular bodies (arrows); with additional labeling in the endoplasmic reticulum, Golgi complex and intracellular vesicles (panels A, C, arrows). In panel B a small SEL1L-labeled multivesicular body (arrow) lies in direct apposition to the plasma membrane. Exosomal-like vesicles, that seem to originate from fusion of this multivesicular body with the plasma membrane, bud into the extracellular space (arrowhead), suggesting that SEL1L is secreted via exosomes derived from the multivesicular body. Bars: 0.1 µm; er: endoplasmic reticulum; G: Golgi apparatus; MVB: multivesicular body; PM: plasma membrane.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040770&req=5

pone-0017206-g005: Localizations of SEL1L in MG132-treated KMS11 cells.Cryoimmunogold electron microscopy of MG132-treated cells labeled with 15 nm gold for SEL1L N-terminus shows SEL1L localized mainly in internal vesicles of multivesicular bodies (arrows); with additional labeling in the endoplasmic reticulum, Golgi complex and intracellular vesicles (panels A, C, arrows). In panel B a small SEL1L-labeled multivesicular body (arrow) lies in direct apposition to the plasma membrane. Exosomal-like vesicles, that seem to originate from fusion of this multivesicular body with the plasma membrane, bud into the extracellular space (arrowhead), suggesting that SEL1L is secreted via exosomes derived from the multivesicular body. Bars: 0.1 µm; er: endoplasmic reticulum; G: Golgi apparatus; MVB: multivesicular body; PM: plasma membrane.
Mentions: Correspondingly, in MG132-treated KMS11 cells, IEM showed that SEL1L was present in vesicles dispersed in the peripheral cytoplasm or associated with late endosomes/MVBs (Figure 5A, C). Furthermore, in areas where MVBs were adjacent to the PM, SEL1L-labeled vesicles appeared to emerge into the extracellular space (Figure 5B).

Bottom Line: We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28.Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA.P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biomedical Technologies, National Research Council, Milan, Italy.

ABSTRACT
We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28. Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA. P38 is expressed and constitutively secreted, with increase after ER stress, in the KMS11 myeloma line and in the breast cancer lines MCF7 and SKBr3, but not in the non-tumorigenic breast epithelial MCF10A line. P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress. Consistently with the presence of p38 and p28 in culture media, morphological studies of SKBr3 and KMS11 cells detect N-terminal SEL1L immunolabeling in secretory/degradative compartments and extracellularly-released membrane vesicles. Our findings suggest that the two new SEL1L variants are engaged in endosomal trafficking and secretion via vesicles, which could contribute to relieve ER stress in tumorigenic cells. P38 and p28 could therefore be relevant as diagnostic markers and/or therapeutic targets in cancer.

Show MeSH
Related in: MedlinePlus