PXD038912

PXD038912 is an original dataset announced via ProteomeXchange.

Title	NDR kinase Tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development
Description	The GckIII pathway is a Hippo-like kinase module defined by sequential activation of Ste20 kinases Thousand and One (Tao) and Germinal Center Kinase III (GckIII), followed by nuclear dbf2-related (NDR) kinase Tricornered (Trc). We previously uncovered a role for the GckIII pathway in regulating tube morphology in the Drosophila melanogaster tracheal (respiratory) system. The trachea form a network of branched epithelial tubes essential for oxygen transport, and are structurally analogous to branched tubular organs in vertebrates, such as the vascular system. In the absence of GckIII pathway function, aberrant dilations form in tracheal tubes characterised by mislocalized junctional and apical proteins, suggesting that the GckIII pathway is important in maintaining tube integrity in development. Here, we observed a genetic interaction between trc and Cerebral cavernous malformations 3 (Ccm3), the Drosophila ortholog of a human vascular disease gene, supporting our hypothesis that the GckIII pathway functions downstream of Ccm3 in trachea, and potentially in the vertebrate cerebral vasculature. However, how GckIII pathway signalling is regulated and the mechanisms that underpin its function in tracheal development are unknown. We undertook biochemical and genetic approaches to identify proteins that interact with Trc, the most downstream GckIII pathway kinase. We found that known GckIII and NDR scaffold proteins are likely to control GckIII pathway signalling in tracheal development, consistent with their conserved roles in Hippo-like modules. Furthermore, we show genetic interactions between trc and multiple enzymes in glycolysis and oxidative phosphorylation, suggesting a potential function of the GckIII pathway in integrating cellular energy requirements with maintenance of tube integrity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:17.541.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexey Veraksa
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-19 03:15:42	ID requested
1	2023-03-13 16:45:19	announced
⏵ 2	2023-11-14 08:44:25	announced	2023-11-14: Updated project metadata.

Hudson J, Paul S, Veraksa A, Ghabrial A, Harvey KF, Poon C, NDR kinase tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development. G3 (Bethesda), 13(3):(2023) [pubmed]

submitter keyword: trachea,Drosophila, NDR kinase, Tricornered

Alexey Veraksa
contact affiliation	Biology Department University of Massachusetts Boston Boston, USA
contact email	alexey.veraksa@umb.edu
lab head
Alexey Veraksa
contact affiliation	University of Massachusetts Boston
contact email	alexey.veraksa@umb.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038912
     1. Label: PRIDE project
     2. Name: NDR kinase Tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development