| Title |
Conserved ectodomain cysteines are essential for rat P2X7 receptor trafficking
|
|---|---|
| Published in |
Purinergic Signalling, January 2012
|
| DOI | 10.1007/s11302-012-9291-x |
| Pubmed ID | |
| Authors |
Marie Jindrichova, Pavlo Kuzyk, Shuo Li, Stanko S. Stojilkovic, Hana Zemkova |
| Abstract |
The P2X7 receptor (P2X7R) is a member of the ATP-gated ion channel family that exhibits distinct electrophysiological and pharmacological properties. This includes low sensitivity to ATP, lack of desensitization, a sustained current growth during prolonged receptor stimulation accompanied with development of permeability to large organic cations, and the coupling of receptor activation to cell blebbing and death. The uniquely long C-terminus of P2X7R accounts for many of these receptor-specific functions. The aim of this study was to understand the role of conserved ectodomain cysteine residues in P2X7R function. Single- and double-point threonine mutants of C119-C168, C129-C152, C135-C162, C216-C226, and C260-C269 cysteine pairs were expressed in HEK293 cells and studied using whole-cell current recording. All mutants other than C119T-P2X7R responded to initial and subsequent application of 300-μM BzATP and ATP with small amplitude monophasic currents or were practically nonfunctional. The mutagenesis-induced loss of function was due to decreased cell-surface receptor expression, as revealed by assessing levels of biotinylated mutants. Coexpression of all double mutants with the wild-type receptor had a transient or, in the case of C119T/C168T double mutant, sustained inhibitory effect on receptor trafficking. The C119T-P2X7R mutant was expressed on the plasma membrane and was fully functional with a slight decrease in the sensitivity for BzATP, indicating that interaction of liberated Cys168 with another residue rescues the trafficking of receptor. Thus, in contrast to other P2XRs, all disulfide bonds of P2X7R are individually essential for the proper receptor trafficking. |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 6% |
| Italy | 1 | 6% |
| Unknown | 16 | 89% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 33% |
| Researcher | 5 | 28% |
| Student > Doctoral Student | 1 | 6% |
| Professor > Associate Professor | 1 | 6% |
| Student > Postgraduate | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 4 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 33% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 11% |
| Biochemistry, Genetics and Molecular Biology | 2 | 11% |
| Immunology and Microbiology | 1 | 6% |
| Neuroscience | 1 | 6% |
| Other | 2 | 11% |
| Unknown | 4 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 April 2013.
All research outputs
#7,169,715
of 22,662,201 outputs
Outputs from Purinergic Signalling
#86
of 373 outputs
Outputs of similar age
#68,817
of 246,880 outputs
Outputs of similar age from Purinergic Signalling
#2
of 4 outputs
Altmetric has tracked 22,662,201 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 373 research outputs from this source. They receive a mean Attention Score of 3.0. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 246,880 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.