The Role of a Conserved Inter-Transmembrane Domain Interface in Regulating α2a-Adrenergic Receptor Conformational Stability and Cell-Surface Turnover

The ubiquitous Na,K- and the gastric H,K-pumps are heterodimeric plasma membrane proteins composed of an alpha and a beta subunit. The H,K-ATPase beta subunit (beta HK) can partially act as a surrogate for the Na,K-ATPase beta subunit (beta NK) in the formation of functional Na,K-pumps (Horisberger et al., 1991. J. Biol. Chem. 257:10338-10343). We have examined the role of the transmembrane and/or the ectodomain of beta NK in (a) its ER retention in the absence of concomitant synthesis of Na,K-ATPase alpha subunits (alpha NK) and (b) the functional expression of Na,K-pumps at the cell surface and their activation by external K+. We have constructed chimeric proteins between Xenopus beta NK and rabbit beta HK by exchanging their NH2-terminal plus transmembrane domain with their COOH-terminal ectodomain (beta NK/HK, beta HK/NK). We have expressed these constructs with or without coexpression of alpha NK in the Xenopus oocyte. In the absence of alpha NK, Xenopus beta NK and all chimera that contained the ectodomain of beta NK were retained in the ER while beta HK and all chimera with the ectodomain of beta HK could leave the ER suggesting that ER retention of unassembled Xenopus beta NK is mediated by a retention signal in the ectodomain. When coexpressed with alpha NK, only beta NK and beta NK/HK chimera assembled efficiently with alpha NK leading to similar high expression of functional Na,K-pumps at the cell surface that exhibited, however, a different apparent K+ affinity. beta HK or chimera with the transmembrane domain of beta HK assembled less efficiently with alpha NK leading to lower expression of functional Na,K-pumps with a different apparent K+ affinity. The data indicate that the transmembrane domain of beta NK is important for efficient assembly with alpha NK and that both the transmembrane and the ectodomain of beta subunits play a role in modulating the transport activity of Na,K-pumps.

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The Role of the Interaction between Fe(III) and Cell Surface in the Accumulation of 67Ga by Tumor Cells

Nuklearmedizin ◽

10.1055/s-0038-1629590 ◽

1991 ◽

Vol 30 (06) ◽

pp. 290-293 ◽

Cited By ~ 1

Author(s):

P. Maleki ◽

A. Martinezi ◽

M. C. Crone-Escanye ◽

J. Robert ◽

L. J. Anghileri

Keyword(s):

Cell Surface ◽

Tumor Cells ◽

Ionic Composition ◽

Iron Complex ◽

Iron Binding ◽

Complex Time ◽

Interaction Product ◽

Thermodynamic Constant ◽

Number Of Cells

The study of the interaction between complexed iron and tumor cells in the presence of 67Ga-citrate indicates that a phenomenon of iron-binding related to the thermodynamic constant of stability of the iron complex, and a hydrolysis (or anion penetration) of the interaction product determine the uptake of 67Ga. The effects of various parameters such as ionic composition of the medium, nature of the iron complex, time of incubation and number of cells are discussed.

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The Role of the Cell Surface Proteases Meprin A and B in Breast Cancer Progression

10.21236/ada394888 ◽

2001 ◽

Author(s):

Gail L. Matters

Keyword(s):

Breast Cancer ◽

Cell Surface ◽

Cancer Progression ◽

Breast Cancer Progression

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Syndecan Transmembrane Domain Specifically Regulates Downstream Signaling Events of the Transmembrane Receptor Cytoplasmic Domain

International Journal of Molecular Sciences ◽

10.3390/ijms22157918 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7918

Author(s):

Jisun Hwang ◽

Bohee Jang ◽

Ayoung Kim ◽

Yejin Lee ◽

Joonha Lee ◽

...

Keyword(s):

Transmembrane Domain ◽

Growth Factor Receptor ◽

Cytoplasmic Domain ◽

Nih3t3 Cells ◽

C Elegans ◽

Downstream Signaling ◽

Downstream Effectors ◽

Signaling Events

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains unknown. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory effects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, comprising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corresponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior.

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Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

Scientific Reports ◽

10.1038/s41598-021-91184-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Barbara Jana ◽

Jarosław Całka

Keyword(s):

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Domestic Animals ◽

Inhibitory Effect ◽

Receptor Subtypes ◽

Beta Adrenergic Receptor ◽

Pharmacological Modulation ◽

Uterine Inflammation ◽

Myometrial Contractility

AbstractUterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of β1-, β2- and β3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, β1- and β3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, β2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all β-ARs subtypes, however, β2-ARs have the greatest importance. Given this, pharmacological modulation of particular β-ARs subtypes can be used to increase inflamed uterus contractility.

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