PXD046157

PXD046157 is an original dataset announced via ProteomeXchange.

Title	Mechanical control of the splicing regulator PTBP1 regulates extracellular matrix stiffness-induced proliferation and mechanomemory
Description	Cells sense and respond to mechanical cues from their environment. Mechanical cues have been shown to be important for many biological processes, including embryonic development, aging, cellular homeostasis, and diseases. Cells translate mechanical cues into cellular biochemical signals that govern cellular behaviour like proliferation or migration, via a process called mechanotransduction. However this process and the proteins involved remain incompletely understood. Here, we present an unbiased and large scale screen approach to identify proteins involved in mechanotransduction. The screen revealed that the splicing factor PTBP1 is a novel mechanotransducer. We show that the nuclear localisation of PTBP1 depends on the extracellular matrix stiffness, cell density, and the actomyosin-based contractility of the cell. Furthermore, we demonstrate that PTBP1 promotes the mechanosensitive splicing of the adapter protein Numb, and that alternative splicing of Numb is crucial for matrix stiffness-induced proliferation. Our results support the idea that changes in alternative splicing are an integral part of mechanotransduction and provide a mechanism by which matrix stiffness regulates cell proliferation and the formation of a mechanomemory in cells.
HostingRepository	PRIDE
AnnounceDate	2025-03-31
AnnouncementXML	Submission_2025-03-31_03:26:22.182.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-16 03:59:09	ID requested
⏵ 1	2025-03-31 03:26:22	announced

10.1016/J.ISCI.2025.112273;

submitter keyword: PTBP1, mechanotransduction, splicing, extracellular matrix

Mark Collins
contact affiliation	School of Biosciences University of Sheffield Sheffield, S10 2TN United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046157
     1. Label: PRIDE project
     2. Name: Mechanical control of the splicing regulator PTBP1 regulates extracellular matrix stiffness-induced proliferation and mechanomemory