PXD060982

PXD060982 is an original dataset announced via ProteomeXchange.

Title	mTOR orchestrates sequential phases of ependymal cell differentiation by acting on their alternative cell cycle and centrosomal proteins
Description	Ependymal cells are multiciliated cells lining the brain ventricles, which arise from the differentiation of progenitor cells through the phases of centriole amplification, growth and disengagement phases. Since these commitment phases are accompanied by the sharp up-regulation of mTOR complex 1 activity (mTORC1), a master regulator of macromolecule biosynthesis and cell growth, we address its functional role. We show that mTORC1 inhibition by rapamycin maintains the progenitor pool by reinforcing a quiescent state and blocking the alternative cell cycle progression for centriole amplification. Overexpression of E2F4 and Mcidas bypasses the mTORC1-regulated events and rescues centriole amplification even in the presence of rapamycin, while promoting mTORC1 activity in a positive feed-forward mechanism. Acute rapamycin treatment in multicentriolar cells during the late phases of differentiation causes centriole regrouping, indicating a direct role of mTORC1 on centriole dynamics. By phosphoproteomic and phospho-mutant analysis, we reveal that the mTORC1-mediated phosphorylation of Gas2L1, a centrosomal protein linking actin and microtubule cytoskeletons, participates in the centriole disengagement. This multi-layered and sequential control of ependymal development by mTORC1, from the progenitor pool to the centriolar function, has implications for pathophysiological conditions, such as aging and hydrocephalus-prone genetic diseases.
HostingRepository	PRIDE
AnnounceDate	2025-03-14
AnnouncementXML	Submission_2025-03-14_07:20:10.999.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	VONDA KOKA
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-19 15:35:34	ID requested
⏵ 1	2025-03-14 07:20:11	announced

Dataset with its publication pending

submitter keyword: cytoskeleton, ciliogenesis, differentiation,mTOR, cell cycle

Mario Pende
contact affiliation	Université Paris Cité, CNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France
contact email	mario.pende@inserm.fr
lab head
VONDA KOKA
contact affiliation	INEM U1151 INSERM
contact email	vonda.koka@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060982
     1. Label: PRIDE project
     2. Name: mTOR orchestrates sequential phases of ependymal cell differentiation by acting on their alternative cell cycle and centrosomal proteins