scholarly journals cTAGE5 mediates collagen secretion through interaction with TANGO1 at endoplasmic reticulum exit sites

2011 ◽  
Vol 22 (13) ◽  
pp. 2301-2308 ◽  
Author(s):  
Kota Saito ◽  
Koh Yamashiro ◽  
Yuki Ichikawa ◽  
Patrik Erlmann ◽  
Kenji Kontani ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Lymphoma ◽  
Coiled Coil ◽  
Integral Membrane Protein ◽  
Cutaneous T Cell Lymphoma ◽  
Rich Domain ◽  
Collagen Secretion ◽  
Er Exit Sites ◽  
Antigen 5 ◽  
Collagen Vii

Cutaneous T-cell lymphoma-–associated antigen 5 (cTAGE5), an originally identified tumor antigen, is overexpressed in various cancer cell lines. The cDNA encodes an integral membrane protein containing two coiled-coil motifs and a proline-rich domain. We show that cTAGE5 specifically localizes to the endoplasmic reticulum (ER) exit sites. In addition, cTAGE5 forms a complex with TANGO1 (MIA3), a previously characterized cargo receptor for collagen VII, by the interaction of their coiled-coil motifs. Of interest, cTAGE5, as well as TANGO1, is capable of interacting with the inner-layer coatomer of COPII Sec23/24 complex through their C-terminal proline-rich domains and required for collagen VII secretion. We propose that cTAGE5 acts as a coreceptor of TANGO1 for collagen VII export from the ER.

scholarly journals Dual function of cTAGE5 in collagen export from the endoplasmic reticulum

2016 ◽  
Vol 27 (13) ◽  
pp. 2008-2013 ◽  
Author(s):  
Tomoya Tanabe ◽  
Miharu Maeda ◽  
Kota Saito ◽  
Toshiaki Katada
Keyword(s):  
Endoplasmic Reticulum ◽  
Dual Function ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Collagen Secretion ◽  
Nucleotide Exchange Factor ◽  
Independent Functions ◽  
Er Exit Sites ◽  
Gtpase Cycle ◽  
Collagen Vii

Two independent functions of cTAGE5 have been reported in collagen VII export from the endoplasmic reticulum (ER). cTAGE5 not only forms a cargo receptor complex with TANGO1, but it also acts as a scaffold to recruit Sec12, a guanine-nucleotide exchange factor for Sar1 GTPase, to ER exit sites. However, the relationship between the two functions remains unclear. Here we isolated point mutants of cTAGE5 that lost Sec12-binding ability but retained binding to TANGO1. Although expression of the mutant alone could not rescue the defects in collagen VII secretion mediated by cTAGE5 knockdown, coexpression with Sar1, but not with the GTPase-deficient mutant, recovered secretion. The expression of Sar1 alone failed to rescue collagen secretion in cTAGE5-depleted cells. Taken together, these results suggest that two functionally irreplaceable and molecularly separable modules in cTAGE5 are both required for collagen VII export from the ER. The recruitment of Sec12 by cTAGE5 contributes to efficient activation of Sar1 in the vicinity of ER exit sites. In addition, the GTPase cycle of Sar1 appears to be responsible for collagen VII exit from the ER.

scholarly journals Distinct isoform-specific complexes of TANGO1 cooperatively facilitate collagen secretion from the endoplasmic reticulum

2016 ◽  
Vol 27 (17) ◽  
pp. 2688-2696 ◽  
Author(s):  
Miharu Maeda ◽  
Kota Saito ◽  
Toshiaki Katada
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Protein Complex ◽  
Integral Membrane Protein ◽  
Collagen Binding ◽  
Macromolecular Complexes ◽  
Collagen Secretion ◽  
Transport Vesicles ◽  
Er Exit Sites ◽  
Membrane Bound

Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER. Moreover, we found that each of the TANGO1 isoforms forms a stable protein complex with factors involved in collagen secretion: TANGO1L/cTAGE5/Sec12 (900 kDa) and TANGO1S/cTAGE5/Sec12 (700 kDa). Of interest, TANGO1S and TANGO1L seemed to be interchangeable in exporting collagen from the ER. Our results suggest that mammalian ER exit sites possess two different-sized membrane-bound macromolecular complexes that specifically function in large-cargo export from the ER.

scholarly journals Sequential Recruitment of the Endoplasmic Reticulum and Chloroplasts for Plant Potyvirus Replication

2009 ◽  
Vol 84 (2) ◽  
pp. 799-809 ◽  
Author(s):  
Taiyun Wei ◽  
Tyng-Shyan Huang ◽  
Jamie McNeil ◽  
Jean-François Laliberté ◽  
Jian Hong ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Integral Membrane Protein ◽  
Genome Replication ◽  
Transport Pathway ◽  
Er Exit Sites ◽  
Weight Protein ◽  
Infected Cells ◽  
Membrane Bound ◽  
Viral Replicase ◽  
Positive Strand Rna

ABSTRACT The replication of positive-strand RNA viruses occurs in cytoplasmic membrane-bound virus replication complexes (VRCs). Depending on the virus, distinct cellular organelles such as the endoplasmic reticulum (ER), chloroplast, mitochondrion, endosome, and peroxisome are recruited for the formation of VRC-associated membranous structures. Previously, the 6,000-molecular-weight protein (6K) of plant potyviruses was shown to be an integral membrane protein that induces the formation of 6K-containing membranous vesicles at endoplasmic reticulum (ER) exit sites for potyvirus genome replication. Here, we present evidence that the 6K-induced vesicles predominantly target chloroplasts, where they amalgamate and induce chloroplast membrane invaginations. The vesicular transport pathway and actomyosin motility system are involved in the trafficking of the 6K vesicles from the ER to chloroplasts. Viral RNA, double-stranded RNA, and viral replicase components are concentrated at the 6K vesicles that associate with chloroplasts in infected cells, suggesting that these chloroplast-bound 6K vesicles are the site for potyvirus replication. Taken together, these results suggest that plant potyviruses sequentially recruit the ER and chloroplasts for their genome replication.

The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors

2009 ◽  
Vol 418 (2) ◽  
pp. 293-310 ◽  
Author(s):  
Yiguo Zhang ◽  
John M. Lucocq ◽  
John D. Hayes
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Envelope ◽  
Brefeldin A ◽  
Integral Membrane Protein ◽  
Subcellular Fractionation ◽  
Multiple Point ◽  
Related Factor ◽  
Rich Domain ◽  
Membrane Microdomain ◽  
Type Factor

In rat liver RL-34 cells, endogenous Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is localized in the ER (endoplasmic reticulum) where it exists as a glycosylated protein. Electron microscopy has demonstrated that ectopic Nrf1 in COS-1 cells is located in the ER and the NE (nuclear envelope). Subcellular fractionation, together with a membrane proteinase protection assay, revealed that Nrf1 is an integral membrane protein with both luminal and cytoplasmic domains. The N-terminal 65 residues of Nrf1 direct its integration into the ER and NE membranes and tether it to a Triton X-100-resistant membrane microdomain that is associated with lipid rafts. The activity of Nrf1 was increased by the electrophile tBHQ (t-butyl hydroquinone) probably through an N-terminal domain-dependent process. We found that the NST (Asn/Ser/Thr-rich) domain, along with AD1 (acidic domain 1), contributes positively to the transactivation activity of full-length Nrf1. Furthermore, the NST domain contains seven putative -Asn-Xaa-Ser/Thr- glycosylation sites and, when glycosylation was prevented by replacing all of the seven asparagine residues with either glutamine (Nrf11–7×N/Q) or aspartic acid (Nrf11–7×N/D), the former multiple point mutant possessed less activity than the wild-type factor, whereas the latter mutant exhibited substantially greater activity. Lastly, the ER stressors tunicamycin, thapsigargin and Brefeldin A were found to inhibit basal Nrf1 activity by ∼25%, and almost completely prevented induction of Nrf1-mediated transactivation by tBHQ. Collectively, these results suggest that the activity of Nrf1 critically depends on its topology within the ER, and that this is modulated by redox stressors, as well as by its glycosylation status.

scholarly journals Tango1 spatially organizes ER exit sites to control ER export

2017 ◽  
Vol 216 (4) ◽  
pp. 1035-1049 ◽  
Author(s):  
Min Liu ◽  
Zhi Feng ◽  
Hongmei Ke ◽  
Ying Liu ◽  
Tianhui Sun ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Close Proximity ◽  
Melanoma Inhibitory Activity ◽  
Er Exit Sites ◽  
Center Loss ◽  
Er Export ◽  
Multiple Interactions ◽  
Secretory Capacity

Exit of secretory cargo from the endoplasmic reticulum (ER) takes place at specialized domains called ER exit sites (ERESs). In mammals, loss of TANGO1 and other MIA/cTAGE (melanoma inhibitory activity/cutaneous T cell lymphoma–associated antigen) family proteins prevents ER exit of large cargoes such as collagen. Here, we show that Drosophila melanogaster Tango1, the only MIA/cTAGE family member in fruit flies, is a critical organizer of the ERES–Golgi interface. Tango1 rings hold COPII (coat protein II) carriers and Golgi in close proximity at their center. Loss of Tango1, present at ERESs in all tissues, reduces ERES size and causes ERES–Golgi uncoupling, which impairs secretion of not only collagen, but also all other cargoes we examined. Further supporting an organizing role of Tango1, its overexpression creates more and larger ERESs. Our results suggest that spatial coordination of ERES, carrier, and Golgi elements through Tango1’s multiple interactions increases secretory capacity in Drosophila and allows secretion of large cargo.

TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum

2019 ◽  
Vol 476 (21) ◽  
pp. 3241-3260
Author(s):  
Sindhu Wisesa ◽  
Yasunori Yamamoto ◽  
Toshiaki Sakisaka
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Transmembrane Domains ◽  
Domain Family ◽  
Coiled Coil Domain ◽  
U2os Cells ◽  
Er Membrane

The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.

Cutaneous T-Cell Lymphoma Incidence Rising

2008 ◽  
Vol 39 (6) ◽  
pp. 15
Author(s):  
BRUCE JANCIN
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma
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