scholarly journals Dimerization of the Polymeric Immunoglobulin Receptor Controls Its Transcytotic Trafficking

1998 ◽  
Vol 9 (4) ◽  
pp. 901-915 ◽  
Author(s):  
Karen L. Singer ◽  
Keith E. Mostov
Keyword(s):  
Transmembrane Domain ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Glycophorin A ◽  
Polymeric Immunoglobulin Receptor ◽  
Receptor Dimerization ◽  
Immunoglobulin Receptor ◽  
Receptor Oligomerization ◽  
Necessary And Sufficient

Binding of dimeric immunoglobulin (Ig)A to the polymeric Ig receptor (pIgR) stimulates transcytosis of pIgR across epithelial cells. Through the generation of a series of pIgR chimeric constructs, we have tested the ability of ligand to promote receptor dimerization and the subsequent role of receptor dimerization on its intracellular trafficking. Using the cytoplasmic domain of the T cell receptor-ζ chain as a sensitive indicator of receptor oligomerization, we show that a pIgR:ζ chimeric receptor expressed in Jurkat cells initiates a ζ-specific signal transduction cascade when exposed to dimeric or tetrameric IgA, but not when exposed to monomeric IgA. In addition, we replaced the pIgR’s transmembrane domain with that of glycophorin A to force dimerization or with a mutant glycophorin transmembrane domain to prevent dimerization. Forcing dimerization stimulated transcytosis of the chimera, whereas preventing dimerization abolished ligand-stimulated transcytosis. We conclude that binding of dimeric IgA to the pIgR induces its dimerization and that this dimerization is necessary and sufficient to stimulate pIgR transcytosis.

scholarly journals A Role for Fis1 in Both Mitochondrial and Peroxisomal Fission in Mammalian Cells

2005 ◽  
Vol 16 (11) ◽  
pp. 5077-5086 ◽  
Author(s):  
Annett Koch ◽  
Yisang Yoon ◽  
Nina A. Bonekamp ◽  
Mark A. McNiven ◽  
Michael Schrader
Keyword(s):  
Mammalian Cells ◽  
Small Interfering Rna ◽  
Transmembrane Domain ◽  
Mitochondrial Fission ◽  
Ectopic Expression ◽  
Mammalian Homologue ◽  
Necessary And Sufficient ◽  
Interfering Rna ◽  
Peroxisome Division

The mammalian dynamin-like protein DLP1/Drp1 has been shown to mediate both mitochondrial and peroxisomal fission. In this study, we have examined whether hFis1, a mammalian homologue of yeast Fis1, which has been shown to participate in mitochondrial fission by an interaction with DLP1/Drp1, is also involved in peroxisomal growth and division. We show that hFis1 localizes to peroxisomes in addition to mitochondria. Through differential tagging and deletion experiments, we demonstrate that the transmembrane domain and the short C-terminal tail of hFis1 is both necessary and sufficient for its targeting to peroxisomes and mitochondria, whereas the N-terminal region is required for organelle fission. hFis1 promotes peroxisome division upon ectopic expression, whereas silencing of Fis1 by small interfering RNA inhibited fission and caused tubulation of peroxisomes. These findings provide the first evidence for a role of Fis1 in peroxisomal fission and suggest that the fission machinery of mitochondria and peroxisomes shares common components.

Histone Modifier Differentially Regulates Gene Expression and Unravels Survival Role of MicroRNA-494 in Jurkat Leukemia

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Arathi Jayaraman ◽  
Tong Zhou ◽  
Sundararajan Jayaraman
Keyword(s):  
T Cell ◽  
Trichostatin A ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Drug Induced ◽  
Protein Coding ◽  
Qrt Pcr ◽  
Protein Coding Genes ◽  
Histone Hyperacetylation

Background: Although the protein-coding genes are subject to histone hyperacetylation-mediated regulation, it is unclear whether microRNAs are similarly regulated in the T cell leukemia Jurkat. Objective: To determine whether treatment with the histone modifier Trichostatin A could concurrently alter the expression profiles of microRNAs and protein-coding genes. Methods: Changes in histone hyperacetylation and viability in response to drug treatment were analyzed, respectively, using western blotting and flow cytometry. Paired global expression profiling of microRNAs and coding genes was performed and highly regulated genes validated by qRT-PCR. The interrelationships between the drug-induced miR-494 upregulation, the expression of putative target genes, and T cell receptor-mediated apoptosis were evaluated using qRT-PCR, flow cytometry, and western blotting following lipid-mediated transfection with specific anti-microRNA inhibitors. Results: Treatment of Jurkat cells with Trichostatin A resulted in histone hyperacetylation and apoptosis. Global expression profiling indicated prominent upregulation of miR-494 in contrast to differential regulation of many protein-coding and non-coding genes validated by qRT-PCR. Although transfection with synthetic anti-miR-494 inhibitors failed to block drug-induced apoptosis or miR-494 upregulation, it induced the transcriptional repression of the PVRIG gene. Surprisingly, miR-494 inhibition in conjunction with low doses of Trichostatin A enhanced the weak T cell receptor-mediated apoptosis, indicating a subtle pro-survival role of miR-494. Interestingly, this pro-survival effect was overwhelmed by mitogen-mediated T cell activation and higher drug doses, which mediated caspase-dependent apoptosis. Conclusion: Our results unravel a pro-survival function of miR-494 and its putative interaction with the PVRIG gene and the apoptotic machinery in Jurkat cells.

Role of nuclear factor-??B in the expression by tumor necrosis factor-? of the human polymeric immunoglobulin receptor ( pIgR ?) gene

2000 ◽  
Vol 51 (4-5) ◽  
pp. 289-295 ◽  
Author(s):  
N. Takenouchi-Ohkubo ◽  
T. Takahashi ◽  
M. Tsuchiya ◽  
J. Mestecky ◽  
Z. Moldoveanu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Polymeric Immunoglobulin Receptor ◽  
Nuclear Factor ◽  
Factor B ◽  
Immunoglobulin Receptor ◽  
Necrosis Factor

scholarly journals Rotational Coupling of the Transmembrane and Kinase Domains of the Neu Receptor Tyrosine Kinase

2000 ◽  
Vol 11 (10) ◽  
pp. 3589-3599 ◽  
Author(s):  
Charlotte A. Bell ◽  
John A. Tynan ◽  
Kristen C. Hart ◽  
April N. Meyer ◽  
Scott C. Robertson ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Transmembrane Domain ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Receptor Dimerization ◽  
Activating Mutations ◽  
Rotational Coupling ◽  
Specific Orientation

Ligand binding to receptor tyrosine kinases (RTKs) regulates receptor dimerization and activation of the kinase domain. To examine the role of the transmembrane domain in regulation of RTK activation, we have exploited a simplified transmembrane motif, [VVVEVVV]n, previously shown to activate the Neu receptor. Here we demonstrate rotational linkage of the transmembrane domain with the kinase domain, as evidenced by a periodic activation of Neu as the dimerization motif is shifted across the transmembrane domain. These results indicate that activation requires a specific orientation of the kinase domains with respect to each other. Results obtained with platelet-derived growth factor receptor-β suggest that this rotational linkage of the transmembrane domain to the kinase domain may be a general feature of RTKs. These observations suggest that activating mutations in RTK transmembrane and juxtamembrane domains will be limited to those residues that position the kinase domains in an allowed rotational conformation.

The role of T-cell receptor dimerization in T-cell activation

1999 ◽  
Vol 20 (12) ◽  
pp. 568-576 ◽  
Author(s):  
Martin F. Bachmann ◽  
Pamela S. Ohashi
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Receptor Dimerization

scholarly journals Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

2021 ◽  
Vol 22 (5) ◽  
pp. 2284
Author(s):  
Hao Wei ◽  
Ji-Yang Wang
Keyword(s):  
Molecular Chaperone ◽  
Recent Progress ◽  
Marginal Zone ◽  
Specific Protein ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Chaperone Protein ◽  
Apical Side

Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.

scholarly journals Transmembrane Domain–Dependent Functional Oligomerization of Syndecans

2006 ◽  
Vol 6 ◽  
pp. 457-459 ◽  
Author(s):  
Jae Youn Yi ◽  
Innoc Han ◽  
Eok-Soo Oh
Keyword(s):  
Cell Adhesion ◽  
Transmembrane Domain ◽  
Receptor Activation ◽  
Surface Adhesion ◽  
Exact Role ◽  
Receptor Dimerization ◽  
Adhesion Receptor ◽  
Functional Roles ◽  
Cell Adhesion Receptor

Cell surface adhesion receptors of the syndecan family initiate intracellular events through clustering of receptors. This crucial clustering occurs through receptor dimerization or oligomerization, which is mediated by receptor transmembrane domains. However, the exact role of the transmembrane domain during receptor activation is not fully understood. Researchers have not yet determined whether the transmembrane domain functions solely in the physical aspects of receptor clustering, or whether the domain has additional functional roles. Here we review recent advances in understanding the functionality of transmembrane domain–dependent oligomerization of syndecan cell adhesion receptor.

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