PXD062975

PXD062975 is an original dataset announced via ProteomeXchange.

Title	CYRI-B loss promotes enlarged mature focal adhesions and restricts microtubule and ERC1 access to the cell leading edge
Description	CYRI proteins promote lamellipodial dynamics by opposing Rac1-mediated activation of the Scar/WAVE complex. This activity also supports resolution of macropinocytic cups, promoting internalisation of surface proteins, including integrins. Here, we show that CYRI-B also promotes focal adhesion maturation and dynamics. Focal adhesions in CYRI-B-depleted cells show accelerated maturation and become excessively large. We probed the composition of these enlarged focal adhesions, using a Bio-ID screen, with paxillin as bait. Our screen revealed changes in adhesion proteins proximal to paxillin suggesting early activation of stress fibre contraction and depletion of the integrin internalisation mediator ERC1. Lack of CYRI-B leads to more stable lamellipodia and accumulation of polymerised actin in stress fibres. This actin acts as a barrier to microtubule targeting for adhesion turnover. Thus, our studies reveal an important connection between lamellipodia dynamics controlled by CYRI-B and microtubule targeting of ERC1 to modulate adhesion maturation and turnover.
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_16:34:34.910.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-15 04:24:08	ID requested
⏵ 1	2025-12-28 16:34:35	announced

10.1242/jcs.263646;

Whitelaw JA, Ghosh S, Lilla S, Nikolaou S, Tweedy L, Fort L, Paul NR, Zanivan S, Gadegaard N, Insall RH, Machesky LM, CYRI-B loss promotes enlarged mature focal adhesions and restricts microtubule and ERC1 access to the cell leading edge. J Cell Sci, 138(22):(2025) [pubmed]

submitter keyword: vinculin, Bio-ID, integrins, actin cytoskeleton, ERC1,Focal adhesions, paxillin, CYRI-B, microtubules

Laura Machesky
contact affiliation	CRUK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK
contact email	lmm202@cam.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062975
     1. Label: PRIDE project
     2. Name: CYRI-B loss promotes enlarged mature focal adhesions and restricts microtubule and ERC1 access to the cell leading edge