RGD Reference Report - Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding. - Rat Genome Database

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Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding.

Authors: Frantz, C  Barreiro, G  Dominguez, L  Chen, X  Eddy, R  Condeelis, J  Kelly, MJ  Jacobson, MP  Barber, DL 
Citation: Frantz C, etal., J Cell Biol. 2008 Dec 1;183(5):865-79. doi: 10.1083/jcb.200804161. Epub 2008 Nov 24.
RGD ID: 11041716
Pubmed: PMID:19029335   (View Abstract at PubMed)
PMCID: PMC2592832   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200804161   (Journal Full-text)

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H(+) efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phosphatidylinositol bisphosphate binding  IPI1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate11041716 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cfl1  (cofilin 1)


Additional Information