PXD041630

PXD041630 is an original dataset announced via ProteomeXchange.

Title	Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis
Description	Tissue mechanical homeostasis, the concept that cells sense mechanical properties and alter rates of ECM synthesis, assembly and degradation, is of broad interest in biology and medicine, but there is little direct support or insight into mechanisms. Tissue mechanical properties such as elasticity and stiffness are determined primarily by the extracellular matrix (ECM). We therefore set out to test the mechanical homeostasis hypothesis by developing mutations in the mechanosensitive protein talin1 that alter cells’ sensing of ECM stiffness. We identified the side-to-side interaction between talin1 rod domain helix bundles 1 and 2 (R1 and R2) as a novel mechanosensitive site. Mutations that decrease the affinity of the interaction result in a leftward shift in cellular stiffness sensing curves, enabling cells to spread and exert tension on softer substrates. Opening of the R1-R2 interface promotes binding of the Arp2/3 subunit ArpC5L, which is required for the altered stiffness sensing. Introduction of these talin mutations into mice resulted in softer tissue in the ascending aorta with less fibrillar collagen and rupture under lower pressure ex vivo. Together, these results demonstrate that altering cellular stiffness sensing results in altered ECM deposition, tissue stiffness and strength, thus providing direct support for the mechanical homeostasis hypothesis. These results also identify a novel mechanosensitive interaction in the talin rod domain that contributes to this mechanism.
HostingRepository	PRIDE
AnnounceDate	2024-07-16
AnnouncementXML	Submission_2024-07-16_10:45:24.740.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-18 12:12:11	ID requested
⏵ 1	2024-07-16 10:45:25	announced

Dataset with its publication pending

submitter keyword: focal adhesions, stiffness-sensing,mechanical homeostasis, extra-cellular matrix, talin

TuKiet Lam
contact affiliation	Keck MS & Proteomics Resource Yale School of Medicine
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041630
     1. Label: PRIDE project
     2. Name: Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis