Transport carriers operating between early compartments in the mammalian secretory pathway have to travel long distances in the cell by mostly relying on the microtubule network and its associated motor proteins. Although anterograde transport from the endoplasmic reticulum (ER) to the Golgi complex is mediated by cytoplasmic dynein, the identity of the motor(s) mediating transport in the retro...

The tumor-associated antigen GA733 is a cell-surface glycoprotein highly expressed in colorectal carcinomas. In this study, 3 recombinant genes were constructed as follows: GA733 tagged to the ER retention sequence KDEL (GA733K), GA733 fused to the immunoglobulin Fc fragment (GA733-Fc), and GA733-Fc fused to the ER retention sequence (GA733-FcK). Agrobacterium-mediated transformation was used t...

Vibrio cholerae and Escherichia coli heat labile toxins (CT and LT) elicit a secretory response from intestinal epithelia by binding apical receptors (ganglioside GM1) and subsequently activating basolateral effectors (adenylate cyclase). We have recently proposed that signal transduction in polarized cells may require transcytosis of toxin-containing membranes (Lencer, W. I., G. Strohmeier, S....

BACKGROUND Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C)) to the pathogenic one (PrP(Sc)). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, P...

Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein that prevents surface CD80/86 expression by retaining the co-stimulatory molecules within th...

Soluble proteins are enriched in the endoplasmic reticulum (ER) by retrograde transport from the Golgi that is mediated by the KDEL receptors. In addition to the classic carboxyl-terminal KDEL motif, a variety of sequence variants are also capable of receptor binding that result in ER localization. Although different ER localization signals that exhibit varying affinities for the KDEL receptors...

Protein quality control in the early secretory pathway is a ubiquitous eukaryotic mechanism for adaptation to endoplasmic reticulum (ER) stress. An ER molecular chaperone, immunoglobulin heavy chain-binding protein (BiP), is one of the essential components in this process. BiP interacts with nascent proteins to facilitate their folding. BiP also plays an important role in preventing aggregation...

The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and its specific receptor CXCR4 plays an important role in oral cancer metastasis. High expression of CXCR4 may help oral squamous cancer cells invade local tissues and metastasize to lymph nodes. No obvious association was observed between CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis ...

The erd2 protein is the receptor responsible for recycling proteins bearing the carboxyl-terminal sequence KDEL (single-letter amino acid code) to the endoplasmic reticulum, following their loss from that organelle by the process of forward transport. To study the interaction of erd2p with the sequence KDEL we have reconstituted binding of erd2p to its ligand in vitro. Binding in vitro exhibits...