PXD010460

PXD010460 is an original dataset announced via ProteomeXchange.

Title	Fam49/CYRI interacts with Rac1 and locally suppresses protrusions
Description	Actin-based protrusions driving cell migration are reinforced through positive feedback, but it is unclear how the cell restricts the eventual size of protrusions, or limits positive signals to allow them to split or retract. We have identified an evolutionarily conserved regulator of the protrusion machinery, which we name CYRI (CYFIP-related Rac interactor). CYRI binds specifically to activated Rac1 via a common motif that is also found in CYFIP, the Domain of Unknown Function DUF1394; we demonstrate that DUF1394 as a new class of Rac1 binding module. CYRI-depleted cells have broad, Scar/WAVE-enriched lamellipodia and display an enhanced duration and extent of pseudopod extension in response to optogenetic Rac1 activation. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE complex to the cell edge and results in short-lived, unproductive protrusions. CYRI dynamically inhibits Scar/WAVE induced actin to focus positive protrusion signals and regulate pseudopod complexity. It therefore behaves like a “local inhibitor” predicted and described in widely accepted mathematical models, but not previously identified in living cells. CYRI is important for processes requiring polarity and plasticity of protrusions, including directional chemotactic migration and polarization of epithelial cysts.
HostingRepository	PRIDE
AnnounceDate	2018-10-08
AnnouncementXML	Submission_2018-10-08_08:42:46.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Dictyostelium discoideum (Slime mold); NCBI TaxID: 44689;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-17 07:13:51	ID requested
⏵ 1	2018-10-08 08:42:47	announced

Fort L, Batista JM, Thomason PA, Spence HJ, Whitelaw JA, Tweedy L, Greaves J, Martin KJ, Anderson KI, Brown P, Lilla S, Neilson MP, Tafelmeyer P, Zanivan S, Ismail S, Bryant DM, Tomkinson NCO, Chamberlain LH, Mastick GS, Insall RH, Machesky LM, Fam49/CYRI interacts with Rac1 and locally suppresses protrusions. Nat Cell Biol, 20(10):1159-1171(2018) [pubmed]

submitter keyword: Cell migration, Lamellipodia, CYFIP-related Rac interactor, Scar/wave complex, Dictiostelium discoideus, GFP-Trap with Formaldehyde Crosslinking

Sara Rossana Zanivan
contact affiliation	CRUK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/10/PXD010460

PRIDE project URI

• PRIDE
  1. PXD010460
     1. Label: PRIDE project
     2. Name: Fam49/CYRI interacts with Rac1 and locally suppresses protrusions