TCRζ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

Dietrich, Jes; Kastrup, Jesper; Lauritsen, Jens Peter H.; Menné, Charlotte; Bülow, Fritz von; Geisler, Carsten

doi:10.1002/(sici)1521-4141(199905)29:05<1719::aid-immu1719>3.0.co;2-m

Cited by 43 publications

(32 citation statements)

References 35 publications

(15 reference statements)

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“…Perinuclear anti-CD3ε staining is something we have observed earlier6 and Jurkat T cells with undetectable CD3 surface expression have recently been reported34. Moreover, both TCRα and CD3ε have been reported to localise to the perinuclear membrane in addition to intracellular vesicles and the cell surface4647 even if none of these studies used synchronised cells. Together the data suggest that not only CD3ε, but the entire TCR-CD3 complex, relocates to the perinuclear membrane during cell cycle progression to the S-phase and that signalling predominantly occurs during the G1-phase.…”

Section: Discussionmentioning

confidence: 50%

The T cell receptor resides in ordered plasma membrane nanodomains that aggregate upon patching of the receptor

Dinić

Riehl

Adler

et al. 2015

Sci Rep

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Two related models for T cell signalling initiation suggest either that T cell receptor (TCR) engagement leads to its recruitment to ordered membrane domains, often referred to as lipid rafts, where signalling molecules are enriched or that ordered TCR-containing membrane nanodomains coalesce upon TCR engagement. That ordered domains form upon TCR engagement, as they do upon lipid raft marker patching, has not been considered. The target of this study was to differentiate between those three options. Plasma membrane order was followed in live T cells at 37 °C using laurdan to report on lipid packing. Patching of the TCR that elicits a signalling response resulted in aggregation, not formation, of ordered plasma membrane domains in both Jurkat and primary T cells. The TCR colocalised with actin filaments at the plasma membrane in unstimulated Jurkat T cells, consistent with it being localised to ordered membrane domains. The colocalisation was most prominent in cells in G1 phase when the cells are ready to commit to proliferation. At other cell cycle phases the TCR was mainly found at perinuclear membranes. Our study suggests that the TCR resides in ordered plasma membrane domains that are linked to actin filaments and aggregate upon TCR engagement.

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Section: Discussionmentioning

confidence: 50%

The T cell receptor resides in ordered plasma membrane nanodomains that aggregate upon patching of the receptor

Dinić

Riehl

Adler

et al. 2015

Sci Rep

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“…The experiments presented here clearly demonstrate that all assembly steps can occur within the ER. However, recent work from Geisler and co-workers (Dietrich et al, 1999) has shown that in Jurkat T-cell mutants lacking various TCR-CD3 Figure 5 Stoichiometry of a TCR-CD3 assembly intermediate lacking the z chain. Assembly reactions were carried out as in previous experiments using mRNAs encoding all subunits with the exception of the z chain.…”

Section: Stoichiometry Of Key Assembly Intermediatesmentioning

confidence: 99%

Stoichiometry of the T-cell receptor–CD3 complex and key intermediates assembled in the endoplasmic reticulum

Call

Pyrdol

Wucherpfennig

2004

EMBO J

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The T-cell receptor (TCR)-CD3 complex is critical for T-cell development and function, and represents one of the most complex transmembrane receptors. Models of different stoichiometry and valency have been proposed based on cellular experiments and these have important implications for the mechanisms of receptor triggering. Since determination of receptor stoichiometry in T-cells is not possible due to the presence of previously synthesized, unlabeled receptor components with different half-lives, we examined the stoichiometry of the receptor assembled in endoplasmic reticulum (ER) microsomes of B-cell origin. The stoichiometric relationship among all subunits was directly determined using intact radiolabeled TCR-CD3 complexes that were isolated with a sequential, non-denaturing immunoprecipitation method, and identical results were obtained with two detergents belonging to different structural classes. The results firmly establish that the alphabeta TCR-CD3 complex assembled in the ER is monovalent and composed of one copy of the TCRalphabeta, CD3deltaepsilon, CD3gammaepsilon and zeta-zeta dimers.

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“…Golgi apparatus restriction is not uncommon. The TCR is retained in the Golgi until oligomerization is completed [56], viral proteins are retained in the Golgi apparatus [57], and a variety of glycosyltransferases resides in the Golgi apparatus [58]. ␤1-integrins have been shown to be confined to the ER/Golgi apparatus prior to surface expression [51].…”

Section: Discussionmentioning

confidence: 99%

“…Examples of heterodimerization relieving Golgi apparatus retention also exist in the literature. Efficient TCR cell-surface expression requires complete assembly of TCR components [64], as the TCR homodimer is retained in the Golgi apparatus until it associates with the assembled CD3␥ variable receptor heterodimer-CD3␦ complex, resulting in release of TCR Golgi apparatus retention and subsequent relocalization to the cell surface [56]. Thus, CD11d and CD18 surface expression falls into a generally recognized mechanism of retaining individual subunits intracellularly until a functional protein can be trafficked to the cell surface.…”

Section: Discussionmentioning

confidence: 99%

“…By analyzing the surface expression of the domain-swapping chimeras, we showed that the extracellular domain of CD11d is responsible for the observed intracellular retention of CD11d to the TGN in heterologous cells that do not coexpress CD18. Retention of proteins in the Golgi has been reported [56], but the majority of such Golgi retention motifs are located most often in the intracellular domain [66] or transmembrane domain [67] of the protein. However, there are examples of protein extracellular domains mediating intracellular retention [68].…”

Section: Discussionmentioning

confidence: 99%

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The extracellular domain of CD11d regulates its cell surface expression

McKillop

Barrett

Pasternak³

et al. 2009

Journal of Leukocyte Biology

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A mAb targeting the CD11d subunit of the leukocyte integrin CD11d/CD18 decreases intraspinal inflammation and oxidative damage leading to improved neurological outcomes in rodent models of SCI. CD11d/CD18 is the fourth member of the beta2-integrin family. Current evidence indicates that CD11d/CD18 is regulated differently than other beta2-integrins, suggesting that CD11d(+) leukocytes play a distinct role in inflammation. Although the transcriptional control of CD11d expression has been evaluated, control of the intracellular distribution of CD11d has not been addressed. For this reason and as a result of the potential of CD11d as a therapeutic target for SCI and possibly other CNS injuries, we investigated the intracellular localization and surface expression of CD11d in cultured cells. CD11d and CD18 were fused at their C-termini with YFP and mRFP, respectively. Flow cytometry and confocal microscopy demonstrated that rCD11d-YFP is expressed on the cell surface of leukocyte cell lines expressing CD18. In contrast, in heterologous cell lines, CD11d-YFP is retained intracellularly in the TGN. Coexpression of CD11d-YFP and CD18-mRFP relieves this intracellular restriction and allows the CD11d/CD18 heterodimer to be surface-expressed. Based on domain-swapping experiments with CD25, the extracellular domain of CD11d is required and sufficient for the observed intracellular retention in heterologous cells. Furthermore, the transmembrane and C-terminus are also required for proper heterodimerization with CD18 and localization to the plasma membrane. These findings suggest that multiple CD11d domains play a role in controlling intracellular location and association with CD18.

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TCRζ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

Cited by 43 publications

References 35 publications

The T cell receptor resides in ordered plasma membrane nanodomains that aggregate upon patching of the receptor

The T cell receptor resides in ordered plasma membrane nanodomains that aggregate upon patching of the receptor

Stoichiometry of the T-cell receptor–CD3 complex and key intermediates assembled in the endoplasmic reticulum

The extracellular domain of CD11d regulates its cell surface expression

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