| 2014 |
TMED7 is required for trafficking of TLR4 from the endoplasmic reticulum to the cell surface through the Golgi. TMED7 forms a stable complex with the ectodomain of TLR4, an interaction requiring the coiled-coil and GOLD domains but not the cytosolic COPII sorting motif of TMED7. Depletion of TMED7 reduces MyD88-dependent TLR4 signaling but not TRIF/TRAM-mediated signaling. Truncated TMED7 lacking the COPII sorting motif or transmembrane domain is mislocalized and causes ligand-independent signaling from intracellularly accumulated receptors. |
Co-immunoprecipitation, domain deletion/truncation analysis, siRNA knockdown, reporter assays for MyD88- and TRIF-dependent signaling, confocal microscopy |
Science Signaling |
High |
25074978
|
| 2012 |
TMED7 inhibits MyD88-independent TLR4 signaling from endosomes. Upon LPS stimulation, TMED7 co-localizes with TRAM and TLR4 in late endosomes. TMED7 is essential for TAG-mediated disruption of the TRAM/TRIF complex and subsequent degradation of TLR4. TMED7 overexpression inhibits TRAM- or LPS-induced IRF3-signaling pathway activation, while TMED7 knockdown enhances RANTES production after LPS stimulation. |
Overexpression and knockdown studies, co-immunoprecipitation, co-localization by confocal microscopy, cytokine ELISA, reporter assays for IRF3 pathway |
Nature Communications |
High |
22426228
|
| 2024 |
The intramembrane protease RHBDL4 negatively regulates TLR4 signaling by triggering degradation of TMED7, thereby counteracting TLR4 transport to the cell surface. TLR4 activation transcriptionally upregulates RHBDL4, creating a negative feedback loop that reduces TLR4 plasma membrane trafficking. This mechanism prevents over-activation of TLR4-dependent signaling during Mycobacterium tuberculosis macrophage infection and alleviates septic shock in a mouse model. |
RHBDL4 gain/loss-of-function, western blotting for TMED7 protein levels, flow cytometry for TLR4 surface expression, cytokine assays, in vitro macrophage infection model, mouse septic shock model |
Nature Communications |
High |
38453906
|
| 2016 |
GAPR-1 (phosphorylated at Ser58 by IRAK1 downstream of MyD88 signaling) interacts with TMED7, and this phosphorylation-dependent interaction impairs TMED7-mediated disruption of the TRAM-TRIF complex, thereby promoting IFN-β and IL-10 secretion downstream of TLR4. |
Co-immunoprecipitation, phosphorylation assay, overexpression/knockdown, ELISA for IFN-β and IL-10 |
Inflammation |
Medium |
26678074
|
| 2023 |
TMED7 interacts with TLR2, TLR4, and TLR5 but not with TLR3 or TLR9 in protein interaction studies. Dominant-negative forms of TMED7 suppress the export of cell-surface TLRs from the ER to the Golgi, establishing TMED7 as a cargo sorting adaptor specifically required for anterograde trafficking of plasma membrane-destined TLRs. |
Protein interaction studies (co-immunoprecipitation/pulldown), dominant-negative TMED7 expression, confocal microscopy for TLR trafficking |
Traffic |
Medium |
37491993
|
| 2010 |
TMED2/p24beta(1) loss in the 99J mouse mutant results in absence of its oligomerization partners TMED7/p24gamma(3) and TMED10/p24delta(1) from affected tissues, demonstrating that TMED7 protein stability/localization depends on TMED2 within hetero-oligomeric p24 complexes. |
ENU mutagenesis mouse model, immunohistochemistry and western blotting for TMED7 and TMED10 protein levels in mutant vs wild-type tissues |
Developmental Biology |
Medium |
20178780
|
| 2009 |
In Xenopus melanotrope cells, transgenic overexpression of p24gamma(3) (TMED7 ortholog) affects endogenous p24gamma(3) levels, reduces cargo (POMC) cleavage rate (suggesting reduced ER-to-Golgi transport), and affects POMC glycosylation, demonstrating a non-redundant role for this p24 subfamily member in early secretory pathway cargo processing distinct from other p24 members. |
Melanotrope cell-specific transgene expression in Xenopus laevis, pulse-chase radiolabeling, glycosylation and sulfation assays, western blotting |
Biology of the Cell |
Medium |
18699773
|
| 2010 |
In Xenopus melanotrope cells, p24gamma(3) (TMED7 ortholog) has a distinct function from its subfamily relative p24gamma(2) in secretory cargo transport, glycosylation, sulfation, and cleavage of POMC, demonstrating functional non-redundancy even among same-subfamily p24 proteins. |
Melanotrope-specific transgene expression in Xenopus, POMC processing assays (glycosylation, sulfation, cleavage) |
Biochimie |
Medium |
21118709
|
| 2015 |
TMED7/p27 localizes specifically to unstacked flattened Golgi cisternae of the Hermes body (cytoplasmic droplet) of epididymal sperm, as determined by quantitative electron microscope gold antibody labeling, and is segregated from the acrosome during spermiogenesis. TMED7-positive vesicles (~50 nm) emanate from these Golgi cisternae, proposed to transport GLUT-3 to the plasma membrane. |
Quantitative electron microscopy immunogold labeling, tandem mass spectrometry, light microscopy immunolocalization |
Open Biology |
Medium |
26311421
|
| 2015 |
During acrosome formation in spermiogenesis, TMED7/p27 is segregated from the acrosome and continues to mark Golgi identity as the Golgi migrates away from the acrosome in later steps of spermatid differentiation. |
Immunofluorescence microscopy, subcellular fractionation, mass spectrometry of germ cell Golgi fractions |
Molecular Biology of the Cell |
Medium |
25808494
|
| 2020 |
In early mouse embryos, AGS3 knockout causes dispersal of TMED7-positive vesicles (tracked by fluorescent protein tagging) and impairs their polarization toward the membrane, with concomitant reduction of E-cadherin (Cdh1) at cell-contact surfaces. This establishes TMED7-positive vesicles as carriers of Cdh1 cargo to the plasma membrane in a process regulated by AGS3/Gαi signaling. |
CRISPR/Cas9 knockout of AGS3, fluorescent protein tagging of TMED7 and TGN46 in mouse embryos, live imaging, immunofluorescence |
Journal of Cell Science |
Medium |
33148610
|
| 2010 |
Knockdown of p24gamma(3)/TMED7 did not alter Aβ secretion or APP processing in cell-based and cell-free assays, indicating TMED7 does not modulate gamma-secretase cleavage of APP (negative result). |
siRNA knockdown, cell-based and cell-free Aβ secretion assays |
Journal of Neurochemistry |
Medium |
20807314
|