The Ubiquitin-Specific Protease Usp4 Regulates the Cell Surface Level of the A2a Receptor

2005 ◽  
Vol 69 (4) ◽  
pp. 1083-1094 ◽  
Author(s):  
Tetyana Milojević ◽  
Veronika Reiterer ◽  
Eduard Stefan ◽  
Vladimir M. Korkhov ◽  
Mario M. Dorostkar ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Level ◽  
A2a Receptor ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Cell Surface Level

Abstract 130: Arginine Methylation of Smad6 Defines Bone-morphogenetic-protein (BMP) Signaling Duration and Intensity

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
JIAN WU ◽  
Olan Jackson-Weaver ◽  
Tingwei Zhang ◽  
Yongchao Gou ◽  
Jian Xu
Keyword(s):  
Complex Formation ◽  
Cell Surface ◽  
Bone Morphogenetic Protein ◽  
Arginine Methylation ◽  
Bmp Signaling ◽  
Type I ◽  
Surface Level ◽  
Inhibitory Function ◽  
Morphogenetic Protein ◽  
Cell Surface Level

Bone-morphogenetic-protein (BMP)/Smads signaling pathway plays crucial role during heart development and vessel angiogenesis. BMP signaling is induced by the binding of BMP ligands (eg. BMP4) to their receptors, which recruit and phosphorylate receptor-Smads (R-Smads, eg. Smad1, Smad5) that form nuclear-transporting complexes with Smad4 for transcriptional regulation. Smad6 is an inhibitory Smad expresses predominantly in atria-ventricular cushion and outflow tract of the developing mouse heart, and expands to valves and great vessels. At the cell surface level, Smad6 binds to BMP type I receptor to block R-Smads recruitment to the receptor. At cytosolic level, Smad6 block Smad1/Smad4 complex formation. In the nucleus, Smad6 represses transcription. How these three levels of regulation are coordinated to inhibit BMP signaling is not known. We previously showed that BMP ligand induces an acute Smad6 methylation at arginine 74 (R74) at the cell surface level by a methyltransferase PRMT1, and methyl-Smad6 dissociates from receptor to allow receptor-induced Smad1/5 phosphorylation and activation. We further identified a delayed methylation on arginine 81 (R81) of Smad6 in the cytosol by PRMT1. We found that R81 methylation is required for BMP signaling-induced recruitment of Smad6 to phosphor-Smad1; it is also required for Smad6 to disrupt phosphor-Smad1/Smad4 complex formation and the following nuclear transportation, as well as for Smad6 to suppress Smad1 targeting gene transactivation. Previous findings indicate that Smad6 binds to type I receptor and Smad1 through its C-terminal region. We examined how arginine methylation in the N-terminal region, regulates the binding properties of C-terminal Smad6. We found that N-terminal Smad6 stabilizes the interaction between C-terminal Smad6 and Smad1 and enhances Smad6 inhibitory function. Disruption of R81 methylation results in loss of inhibitory function because of an increase in binding between N-term and C-term Smad6 that results in a "closed" conformation. In summary, R81 methylation controls Smad6 activity and R81 methylation of Smad6 defines the duration and intensity of BMP-induced Smad1/5 signaling.

Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3

2008 ◽  
Vol 295 (4) ◽  
pp. F889-F900 ◽  
Author(s):  
Sheerazed Boulkroun ◽  
Dorothée Ruffieux-Daidié ◽  
Jean-Jacques Vitagliano ◽  
Olivier Poirot ◽  
Roch-Philippe Charles ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Long Term Effects ◽  
Hek 293 ◽  
Fourfold Increase ◽  
Sorting Nexin ◽  
Cell Surface Biotinylation ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Adjustment of Na+ balance in extracellular fluids is achieved by regulated Na+ transport involving the amiloride-sensitive epithelial Na+ channel (ENaC) in the distal nephron. In this context, ENaC is controlled by a number of hormones, including vasopressin, which promotes rapid translocation of water and Na+ channels to the plasma membrane and long-term effects on transcription of vasopressin-induced and -reduced transcripts. We have identified a mRNA encoding the deubiquitylating enzyme ubiquitin-specific protease 10 (Usp10), whose expression is increased by vasopressin at both the mRNA and the protein level. Coexpression of Usp10 in ENaC-transfected HEK-293 cells causes a more than fivefold increase in amiloride-sensitive Na+ currents, as measured by whole cell patch clamping. This is accompanied by a three- to fourfold increase in surface expression of α- and γ-ENaC, as shown by cell surface biotinylation experiments. Although ENaC is well known to be regulated by its direct ubiquitylation, Usp10 does not affect the ubiquitylation level of ENaC, suggesting an indirect effect. A two-hybrid screen identified sorting nexin 3 (SNX3) as a novel substrate of Usp10. We show that it is a ubiquitylated protein that is degraded by the proteasome; interaction with Usp10 leads to its deubiquitylation and stabilization. When coexpressed with ENaC, SNX3 increases the channel's cell surface expression, similarly to Usp10. In mCCDcl1 cells, vasopressin increases SNX3 protein but not mRNA, supporting the idea that the vasopressin-induced Usp10 deubiquitylates and stabilizes endogenous SNX3 and consequently promotes cell surface expression of ENaC.

scholarly journals Reduced red blood cell surface level of Factor H as a mechanism underlying paroxysmal nocturnal hemoglobinuria

Leukemia ◽  
2020 ◽  
Author(s):  
Lingjun Zhang ◽  
Jin Y. Chen ◽  
Cassandra Kerr ◽  
Brian A. Cobb ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Cell Surface ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Factor H ◽  
Surface Level ◽  
Cell Surface Level

scholarly journals Quantitation of the Cell Surface Level of Ld Resulting in Positive Versus Negative Selection of the 2C Transgenic T Cell Receptor In Vivo

Immunity ◽  
1997 ◽  
Vol 7 (2) ◽  
pp. 233-241 ◽  
Author(s):  
James R Cook ◽  
Eva-Marie Wormstall ◽  
Tara Hornell ◽  
John Russell ◽  
Janet M Connolly ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Negative Selection ◽  
Cell Receptor ◽  
Surface Level ◽  
Cell Surface Level ◽  
Selection Of

scholarly journals Virus Control of Trafficking from Sorting Endosomes

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Sebastian Zeltzer ◽  
Carol A. Zeltzer ◽  
Suzu Igarashi ◽  
Jean Wilson ◽  
Julie G. Donaldson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Human Cytomegalovirus ◽  
Surface Composition ◽  
Surface Proteins ◽  
Endocytic Pathway ◽  
Endocytic Trafficking ◽  
Cargo Proteins ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Sense And Respond

ABSTRACT The maintenance of cell surface proteins is critical to the ability of a cell to sense and respond to information in its environment. As such, modulation of cell surface composition and receptor trafficking is a potentially important target of control in virus infection. Sorting endosomes (SEs) are control stations regulating the recycling or degradation of internalized plasma membrane proteins. Here we report that human cytomegalovirus (HCMV), a ubiquitous betaherpesvirus, alters the fate of internalized clathrin-independent endocytosis (CIE) cargo proteins, retaining them in virally reprogrammed SEs. We show that the small G protein ARF6 (ADP ribosylation factor 6), a regulator of CIE trafficking, is highly associated with SE membranes relative to uninfected cells. Combined with the observation of accumulated CIE cargo at the SE, these results suggest that infection diminishes the egress of ARF6 and its cargo from the SE. Expression of ubiquitin-specific protease 6 (USP6), also known as TRE17, was sufficient to restore ARF6 and some ARF6 cargo trafficking to the cell surface in infected cells. The USP activity of TRE17 was required to rescue both ARF6 and associated cargo from SE retention in infection. The finding that TRE17 expression does not rescue the trafficking of all CIE cargos retained at SEs in infection suggests that HCMV hijacks the normal sorting machinery and selectively sorts specific cargos into endocytic microdomains that are subject to alternative sorting fates. IMPORTANCE Cells maintain their surface composition, take up nutrients, and respond to their environment through the internalization and recycling of cargo at the cell surface through endocytic trafficking pathways. During infection with human cytomegalovirus (HCMV), host endocytic membranes are reorganized into a juxtanuclear structure associated with viral assembly and egress. Less appreciated is the effect of this reorganization on the trafficking of host proteins through the endocytic pathway. We show that HCMV retains internalized cargo and the effector of clathrin-independent endocytosis at sorting endosomes. The retention of some cargo, but not all, was reversed by overexpression of a ubiquitin-specific protease, TRE17. Our results demonstrate that HCMV induces profound reprogramming of endocytic trafficking and influences cargo sorting decisions. Further, our work suggests the presence of a novel ubiquitin-regulated checkpoint for the recycling of cargo from sorting endosome. These findings have important implications for host signaling and immune pathways in the context of HCMV infection.

Carnosic Acid Reverses the Inhibition of ApoE4 on Cell Surface Level of ApoER2 and Reelin Signaling Pathway

2020 ◽  
Vol 73 (2) ◽  
pp. 517-528
Author(s):  
Maoxiao Feng ◽  
Donghai Cui ◽  
Yi Li ◽  
Jian Shi ◽  
Lan Xiang ◽  
...  
Keyword(s):  
Cell Surface ◽  
Signaling Pathway ◽  
Carnosic Acid ◽  
Surface Level ◽  
Reelin Signaling ◽  
Cell Surface Level

scholarly journals The SUMO-Conjugase Ubc9 Prevents the Degradation of the Dopamine Transporter, Enhancing Its Cell Surface Level and Dopamine Uptake

2019 ◽  
Vol 13 ◽  
Author(s):  
Etienne Cartier ◽  
Jennie Garcia-Olivares ◽  
Eric Janezic ◽  
Juan Viana ◽  
Michael Moore ◽  
...  
Keyword(s):  
Cell Surface ◽  
Dopamine Transporter ◽  
Dopamine Uptake ◽  
Surface Level ◽  
Cell Surface Level
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