Dataset Information


Fam49/CYRI interacts with Rac1 and locally suppresses protrusions

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Dictyostelium discoideum  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Disease Free

SUBMITTER: Sergio Lilla  

LAB HEAD: Sara Rossana Zanivan

PROVIDER: PXD010460 | Pride | 2018-10-08


Dataset's files

Action DRS
Dictyostelium discoideum-UNIPROT.fasta Fasta
JOB_R06_071212_CAF_A_001b.raw Raw
JOB_R06_071212_CAF_A_002.raw Raw
JOB_R06_071212_CAF_A_003.raw Raw
JOB_R06_071212_CAF_A_004.raw Raw
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Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamell  ...[more]

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