PXD071589-1

PXD071589 is an original dataset announced via ProteomeXchange.

Title	Phospho proteomic on megalin during cell cycle stages
Description	Mechanistic target of rapamycin (mTOR) signaling pathway controls eukaryotic growth by regulating metabolism, translation, autophagy and cell cycle. Genetic deletion of renal mTORC1 led to a Fanconi-like syndrome with reduction of the renal cortex, tubular epithelial transport and perturbation of the endocytic machinery. Although the main scavenger receptor megalin remained unaltered, a new phosphorylation site at S4577 was found. The identification of the role of this mTORC1-induced phosphorylation on megalin was subject of our analysis. mTORC1-induced megalin phosphorylation reduced endocytosis rate with only minor distribution changes. It augmented the affinity of megalin to the adaptor protein ARH with consecutively increased proteolytic processing of megalin C-terminal domain and favored cell proliferation. During cell mitosis megalin is localized with ARH at the spindle pole. Compared to wildtype cells, megalin-deficient and ARH-deficient cells showed significantly less cell proliferation, and during cytokinesis significantly less ARH or megalin signals, respectively at the pole of intercellular bridges. Both, lysosomal and non-lysosomal (external) nutrient supply influence cell proliferation to different extent. In conclusion, absence of the mTORC1-induced megalin S4577 phosphorylation favors cell growth and clathrin-mediated endocytosis whereas mTORC1-induced megalin phosphorylation at S4577 favors cell proliferation and increases the affinity to the adaptor protein ARH for proper cell division. Especially, during cytokinesis megalin and ARH ensure trafficking of membrane vesicles towards the pole of intercellular bridges most probably for the terminal abscission process.
HostingRepository	PRIDE
AnnounceDate	2026-05-26
AnnouncementXML	Submission_2026-05-26_00:25:25.721.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine von Toerne
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	phosphorylated residue
Instrument	timsTOF Ultra 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-04 13:57:29	ID requested
⏵ 1	2026-05-26 00:25:26	announced

10.1007/S00018-026-06247-5;

submitter keyword: mTORC1,Megalin/LRP2, phospho proteomics, cell cycle, proteolytic cleavage, endocytosis

Franziska Theilig
contact affiliation	Institute of Anatomy Christian-Albrechts-University Kiel, Kiel, Germany
contact email	f.theilig@anat.uni-kiel.de
lab head
Christine von Toerne
contact affiliation	Helmholtz Zentrum München
contact email	vontoerne@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071589
     1. Label: PRIDE project
     2. Name: Phospho proteomic on megalin during cell cycle stages