Back

Optogenetic manipulation of cGMP highlights PDE5 as the predominant cGMP-hydrolyzing PDE in megakaryocytes

Zhang, Y.; Benz, P.; Stehle, D.; Yang, S.; Kurz, H.; Feil, S.; Nagel, G.; Feil, R.; Gao, S.; Bender, M.

2021-11-12 cell biology
10.1101/2021.11.12.468375 bioRxiv
Show abstract

Cyclic guanosine monophosphate (cGMP) signalling plays a fundamental role in many cell types including platelets. cGMP has been implicated in platelet formation, but mechanistic detail about its spatiotemporal regulation in megakaryocytes (MKs) is lacking. We expressed a photo-activated guanylyl cyclase, Blastocladiella emersonii Cyclase opsin (BeCyclop), after viral-mediated gene transfer in bone marrow (BM)-derived MKs to precisely light-modulate cGMP levels. BeCyclop-MKs showed a significantly increased cGMP concentration after illumination, which was strongly dependent on phosphodiesterase (PDE) 5 activity. This finding was corroborated by real-time imaging of cGMP signals which revealed that pharmacological PDE5 inhibition also potentiated nitric oxide (NO) triggered cGMP generation in BM MKs. In summary, we established for the first time optogenetics in primary MKs and identified PDE5 as the predominant PDE regulating cGMP levels in MKs. These findings also demonstrate that optogenetics allows for the precise manipulation of MK biology.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

1
eLife
● 5828 papers in training set
Top 7%
12.6%
Similar papers in this journal
2
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 5%
7.9%
Similar papers in this journal
3
Frontiers in Cell and Developmental Biology
○ 233 papers in training set
Top 0.2%
6.7%
Similar papers in this journal
4
Science Advances
● 1243 papers in training set
Top 4%
6.2%
Similar papers in this journal
5
iScience
○ 1154 papers in training set
Top 3%
4.8%
Similar papers in this journal
6
EMBO Reports
○ 263 papers in training set
Top 1%
3.2%
7
The Journal of Immunology
◐ 166 papers in training set
Top 0.9%
3.2%
8
Scientific Reports
○ 3612 papers in training set
Top 32%
3.2%
9
Life Science Alliance
● 285 papers in training set
Top 1%
3.1%
50% of probability mass above
10
Journal of Biological Chemistry
○ 690 papers in training set
Top 4%
2.4%
11
Journal of Clinical Investigation
● 179 papers in training set
Top 3%
2.1%
12
JCI Insight
● 277 papers in training set
Top 4%
1.7%
13
The FASEB Journal
○ 194 papers in training set
Top 3%
1.7%
14
Cytometry Part A
○ 33 papers in training set
Top 0.2%
1.7%
15
Blood Advances
● 62 papers in training set
Top 0.8%
1.7%
16
Journal of Cellular Physiology
○ 25 papers in training set
Top 0.3%
1.5%
17
EMBO Molecular Medicine
○ 95 papers in training set
Top 1%
1.5%
18
Journal of Cell Science
● 393 papers in training set
Top 3%
1.4%
19
PLOS Biology
● 486 papers in training set
Top 7%
1.1%
20
Cell Communication and Signaling
○ 51 papers in training set
Top 0.7%
1.1%
21
Haematologica
● 25 papers in training set
Top 0.5%
1.0%
22
PLOS ONE
● 5266 papers in training set
Top 55%
1.0%
23
Communications Biology
○ 993 papers in training set
Top 25%
1.0%
24
Blood
● 74 papers in training set
Top 1%
1.0%
25
Journal of Leukocyte Biology
◐ 42 papers in training set
Top 0.7%
1.0%
26
Cells
○ 249 papers in training set
Top 6%
0.9%
27
Cell Death & Disease
147 papers in training set
Top 4%
0.8%
28
Nature Communications
○ 5641 papers in training set
Top 56%
0.8%
29
Frontiers in Immunology
○ 638 papers in training set
Top 9%
0.8%
30
Cell Reports
○ 1498 papers in training set
Top 27%
0.8%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.