The Golgi Protein RCAS1 Controls Cell Surface Expression of Tumor-associated O-Linked Glycan Antigens

Engelsberg, Arne; Hermosilla, Ricardo; Karsten, Uwe; Schülein, Ralf; Dörken, Bernd; Rehm, Armin

doi:10.1074/jbc.m301361200

Cited by 58 publications

(74 citation statements)

References 37 publications

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“…These data indicate that at least a fraction of exosomal GPRC5B proteins originated from the cell surface. Using the same labeling protocol combined with subcellular fractionation in a sucrose gradient, biotinylated GPRC5B-HA protein was recovered from intracellular fractions that also contained RCAS1 (also known as EBAG9), a Golgi-resident protein (43), at 30 min after cell surface labeling (Fig. 4B), demonstrating that GPRC5B proteins are internalized from the cell surface, which likely occurs prior to their release into exosomes.…”

Section: A Fraction Of Gprc5b Proteins Is Internalized From the Cell mentioning

confidence: 99%

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Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex

Kwon

Nacke

et al. 2016

Journal of Biological Chemistry

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Edited by Thomas SöllnerExosomes, 40 -150-nm extracellular vesicles, transport biological macromolecules that mediate intercellular communications. Although exosomes are known to originate from maturation of endosomes into multivesicular endosomes (also known as multivesicular bodies) with subsequent fusion of the multivesicular endosomes with the plasma membrane, it remains unclear how cargos are selected for exosomal release. Using an inducible expression system for the exosome cargo protein GPRC5B and following its trafficking trajectory, we show here that newly synthesized GPRC5B protein accumulates in the Golgi complex prior to its release into exosomes. The L-type lectin LMAN2 (also known as VIP36) appears to be specifically required for the accumulation of GPRC5B in the Golgi complex and restriction of GPRC5B transport along the exosomal pathway. This may occur due to interference with the adaptor protein GGA1-mediated trans Golgi network-to-endosome transport of GPRC5B. The adaptor protein CD2AP-mediated internalization following cell surface delivery appears to contribute to the Golgi accumulation of GPRC5B, possibly in parallel with biosynthetic/secretory trafficking from the endoplasmic reticulum. Our data thus reveal a Golgi-traversing pathway for exosomal release of the cargo protein GPRC5B in which CD2AP facilitates the entry and LMAN2 impedes the exit of the flux, respectively.

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Section: A Fraction Of Gprc5b Proteins Is Internalized From the Cell mentioning

confidence: 99%

“…Given the perinuclear distribution of GPRC5B-HA as well as the co-fractionation of GPRC5B-HA with the Golgi marker RCAS1 (43) (Fig. 4B), we asked whether this structure corresponds to the Golgi complex.…”

Section: A Fraction Of Gprc5b Proteins Is Internalized From the Cell mentioning

confidence: 99%

Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex

Kwon

Nacke

et al. 2016

Journal of Biological Chemistry

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“…The supranuclear positivity could indicate the presence of Golgi apparatus (Ross et al, 1989), because PNA binds many O-linked oligosaccharides containing GalNAc (Spicer and Schulte, 1992) and O-linked glycans are synthesized in the Golgi complex (Engelsberg et al, 2003). The epithelium lining the crypts of the distal colon showed a more complex glycoconjugate pattern than in the cecum.…”

Section: Discussionmentioning

confidence: 99%

Morphometric Features and Glycoconjugate Pattern of Rabbit Intestine are Affected by Particle Size of Pelleted Diets

Desantis

Zizza

Accogli

et al. 2011

The Anatomical Record

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Feed particle size effects on morphology and glycoconjugate pattern was investigated in the rabbit intestine. Rabbits fed with fine particles (2 mm) displayed more irregularly shaped, higher duodenal villi and deeper crypts in distal colon as well as higher number of goblet cells than coarse (8 mm) fed ones. Brush border expressed: (i) in duodenum, neutral/sulfated glycoconjugates and glycans binding MAL II, SNA, Con A than KOH-sialidase-PNA and DBA reactivity in fine and coarse fed rabbits, respectively, (ii) in cecum, mainly sulfoglycans in coarse fed rabbits, MAL II and PNA staining in all samples, and (iii) in distal colon few sulfoglycans and MAL II reactivity. Enterocytes bound MAL II in duodenum, Con A in cecum, DBA, and Con A in distal colon of all rabbits, SNA in distal colon of coarse fed ones. Brunner's glands displayed high presence of acidic/sulfated mucins in fine fed rabbits, neutral glycoconjugates and reactivity with MAL II, SNA, PNA, KOH-sialidase-PNA, and Con A in all rabbits. Goblet cells exhibited: (i) in duodenum neutral and sulfomucins as well as MAL II and KOH-sialidase-PNA staining, than SNA and DBA in fine and coarse fed rabbits, respectively, (ii) in cecum sulfated glycans, MAL II, SNA, KOH-sialidase-PNA, DBA reactivity, and (iii) in distal colon acidic/sulfomucins, MAL II and SNA staining, and DBA reactivity in fine fed specimens. Crypt cells exhibited neutral and PNA reactive glycoconjugates in the cecum. In the distal colon also acidic/sulfated glycans, and MAL II, KOH-sialidase-PNA, DBA; SNA staining showed weaker reactivity in fine fed rabbits, which bound Con A.

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“…We next investigated whether EBAG9 overexpression could alter cell surface glycosylation as previously reported (9), using another mAb clone, 22.1.1, which detects the tumor-associated Tn antigen (22.1.1 antigen) induced on the cell surface (9). As shown in Fig.…”

Section: Cellular Localization Of Full-length and Truncated Ebag9mentioning

confidence: 99%

“…Nakashima et al (6) demonstrated that EBAG9 was a type II membrane protein that had a C-terminal coiled-coil region at the cell surface that could bind to the putative receptor in T cells and NK cells, thereby inducing their apoptotic cell death (6), and named it receptor-binding cancer antigen expressed on SiSo cells (RCAS1). However, Engelsberg et al presented a new finding that EBAG9 was a Golgi-resident protein that modulates cell surface glycosylation by a series of biochemical and cellular imaging analyses (7)(8)(9)(10)(11). They proposed that EBAG9-overexpression might contribute to the antigenicity of tumor cells by generation of the tumor-associated O-linked glycan Tn antigen (for example, 22.1.1 antigen).…”

Section: Introductionmentioning

confidence: 99%

Intracellular estrogen receptor-binding fragment-associated antigen 9 exerts in vivo tumor-promoting effects via its coiled-coil region

Maeyama

Otsu²,

Kubo

et al. 2011

Int J Oncol

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Abstract. Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a tumor-promoting factor of largely unknown function. To assess a causative role of EBAG9 in advanced malignancies, we generated the EG7-OVA and MethA murine tumor cell lines that stably express full-length or truncated EBAG9 protein, using retroviral-mediated gene transduction. Upon subcutaneous inoculation into immunocompetent mice, both cell lines showed marked acceleration of in vivo tumor growth when full-length EBAG9 was overexpressed. Interestingly, deletion of the coiled-coil region, thereby producing truncated EBAG9 protein, abolished the tumor-acceleration effect, establishing the importance of this domain in EBAG9-mediated tumor promotion. However, there was no alteration in in vitro cell proliferation or expression levels of MHC class I and co-stimulatory molecules believed to play a role in immune evasion of tumor cells in these tumor cell lines expressing full-length or truncated EBAG9 protein. Furthermore, both full-length and truncated EBAG9 proteins showed a predominantly cytoplasmic localization in the tumor cells. Collectively, these results suggest that EBAG9 overexpression can be causative in enhancing the malignant properties of tumor cells, and that tumor promotion likely requires EBAG9 intracellular association with as yet unidentified binding partners via the coiled-coil region.

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The Golgi Protein RCAS1 Controls Cell Surface Expression of Tumor-associated O-Linked Glycan Antigens

Cited by 58 publications

References 37 publications

Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex

Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex

Morphometric Features and Glycoconjugate Pattern of Rabbit Intestine are Affected by Particle Size of Pelleted Diets

Intracellular estrogen receptor-binding fragment-associated antigen 9 exerts in vivo tumor-promoting effects via its coiled-coil region

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