PXD007060-3

PXD007060 is an original dataset announced via ProteomeXchange.

Title	Cell rearrangement during angiogenesis requires suppression of actomyosin at cell-cell contacts via PI3-kinase.
Description	Sprouting angiogenesis is a highly dynamic process which relies on the continuous interchange of endothelial cell relative position within the vascular sprout, a process mediated by cell rearrangements. Here we take advantage of a previous identified role of p110a/PI3K regulating endothelial cell motility to address how cell rearrangement and interaction regulate vessel growth. By using advanced fluorescent zebrafish models and a tamoxifen-inducible endothelial-specific gene targeting in the postnatal mouse retina, we demonstrate that inactivation of the p110a isoform of PI3K in endothelial cells is a good model to study cell shuffling in the growing vasculature. We identify that a failure of endothelial cells to rearrange results in cell elongation and inability to stabilize new contacts upon anastomosis. Instead of rearrange, blockade of p110 signaling drive these cells to grow in a three dimension fashion by sending multiple protrusions which lack lumen and fail to stabilize upon anastomosis. Through a combination of in vivo and in vitro approaches together with a global phosphoproteomic screen, we discover that p110a signaling stimulates cell rearrangements by suppressing actomyosin contractility in a myosin light chain phosphatase (MLCP) dependent manner. Together, our findings highlight the importance of cell rearrangement orchestrating several steps within the angiogenic program and uncover a critical role of the p110a/MLCP axis to suppress actomyosin contractility.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:39:33.285.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD007060
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pedro Casado-Izquierdo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; deaminated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-17 05:15:23	ID requested
1	2018-10-02 08:19:05	announced
2	2018-11-20 02:12:01	announced	Updated publication reference for PubMed record(s): 30446640.
⏵ 3	2024-10-22 04:39:34	announced	2024-10-22: Updated project metadata.

Angulo-Urarte A, Casado P, Castillo SD, Kobialka P, Kotini MP, Figueiredo AM, Castel P, Rajeeve V, Mil, à, -Guasch M, Millan J, Wiesner C, Serra H, Muixi L, Casanovas O, Vi, ñ, als F, Affolter M, Gerhardt H, Huveneers S, Belting HG, Cutillas PR, Graupera M, Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility. Nat Commun, 9(1):4826(2018) [pubmed]

10.1038/s41467-018-07172-3;

10.6019/PXD007060;

curator keyword: Biological

submitter keyword: Mascot, Pescal,Phosphoproteomics, QExactive-Plus, Mice

Pedro R. Cutillas
contact affiliation	Centre for Heamato-Oncology / Barts Cancer Institute
contact email	p.cutillas@qmul.ac.uk
lab head
Pedro Casado-Izquierdo
contact affiliation	Cell Signalling
contact email	p.m.casado-izquierdo@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007060
     1. Label: PRIDE project
     2. Name: Cell rearrangement during angiogenesis requires suppression of actomyosin at cell-cell contacts via PI3-kinase.