Cortactin: The Gray Eminence of the Cytoskeleton

Cosen-Binker, Laura Iris; Kapùs, András

doi:10.1152/physiol.00012.2006

Cited by 165 publications

(213 citation statements)

References 101 publications

Supporting

Mentioning

202

Contrasting

Unclassified

Order By: Relevance

“…Cortactin was thought for years to be essential for processes involving Arp2/3 complex function, such as lamellipodia formation or receptor-mediated endocytosis 14 , and the finding that it was dispensable for these processes 10 was quite surprising, albeit consistent with earlier observations e.g. using Drosophila genetics 15 .…”

supporting

confidence: 68%

How distinct Arp2/3 complex variants regulate actin filament assembly

Rottner

Stradal

2015

Nat Cell Biol

View full text Add to dashboard Cite

show abstract

supporting

confidence: 68%

How distinct Arp2/3 complex variants regulate actin filament assembly

Rottner

Stradal

2015

Nat Cell Biol

View full text Add to dashboard Cite

show abstract

“…Subsequently, we found that the mechanism for channel suppression involves the dynamin-dependent endocytosis of Kv1.2 (2). That finding is particularly intriguing because cortactin's role in endocytosis is becoming increasingly apparent (3,4).…”

mentioning

confidence: 89%

An essential role for cortactin in the modulation of the potassium channel Kv1.2

Williams¹,

Markey²,

Doczi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ion channels are key determinants of membrane excitability. The actin cytoskeleton has a central role in morphology, migration, intracellular transport, and signaling. In this article, we show that the actin-binding protein cortactin regulates the potassium channel Kv1.2 and thereby provides a direct link between actin dynamics and membrane excitability. In previous reports, we showed that the tyrosine phosphorylation-mediated suppression of Kv1.2 ionic current occurs by endocytosis of the channel protein. Pull-down assays using recombinant-purified cortactin and Kv1.2 demonstrated that their interaction is direct and reduced by tyrosine phosphorylation of Kv1.2. This finding suggests a link between cortactin and Kv1.2 endocytosis. Here, we confirm that relationship and identify the molecular mechanisms involved. We use FRET to demonstrate that Kv1.2 and cortactin interact in vivo. By manipulating the cortactin-binding site within Kv1.2, we confirm that cortactin proximity influences channel function. We used flow cytometry in conjunction with cortactin gene replacement to identify C-terminal tyrosines, the fourth repeat actin-binding domain, and the N-terminal Arp2/3-binding region, as critical to Kv1.2 regulation. Surprisingly, cortactin's dynamin-binding Src homology 3 domain is not required for Kv1.2 endocytosis, despite that process being dynamin-dependent. These findings predict that cortactin-mediated actin remodeling in excitable cells is not only important for cell structure, but may directly impact membrane excitability.actin ͉ cytoskeleton ͉ endocytosis ͉ excitability ͉ trafficking S uppression of Kv1.2 mediated by the M1 muscarinic receptor was the first example of tyrosine phosphorylation-dependent modulation of voltage-dependent ion channels. Later studies revealed that channel suppression involves the dynamic interaction of Kv1.2 with the actin-binding protein cortactin. Cortactin binds to the N and C termini of Kv1.2, and binding is diminished upon tyrosine phosphorylation of the channel (1). That evidence, along with mutagenesis studies, led to the hypothesis that cortactin was necessary for Kv1.2 function, and that its dissociation contributed to channel suppression. Subsequently, we found that the mechanism for channel suppression involves the dynamin-dependent endocytosis of Kv1.2 (2). That finding is particularly intriguing because cortactin's role in endocytosis is becoming increasingly apparent (3, 4).Since cortactin's discovery, its functions have been correlated with specific structural domains. Cortactin was first described as an actin cross-linking protein enriched within the cell cortex (5), a property requiring the fourth cortactin repeat region. Later studies identified cortactin as an activator of the Arp2/3 complex, a property dependent on a tryptophan residue (W22) within cortactin's N terminus (5). Tyrosine phosphorylation of cortactin's C-terminal region by Src family kinases affects its ability to regulate actin (6), identifying cortactin as a link between tyrosine kinase sign...

show abstract

“…The upstream regulator of Pfn-1 is not well identified. Because cortactin has been implicated in actin cytoskeletal remodeling (13,14), we hypothesized that contractile stimulation may promote the association of cortactin with Pfn-1, which may activate Pfn-1 in smooth muscle in response to contractile activation. To test this, HASM cells were stimulated with ACh (a stimulus implicated in airway tone and asthma) (38) for 5 min, or cells were unstimulated.…”

Section: Interaction Of Cortactin With Pfn-1 Is Enhanced In Smoothmentioning

confidence: 99%

“…Cortactin is an adapter protein that is able to regulate actin filament assembly and branching in in vitro studies as well as adhesion, migration, and endocytosis of nonmuscle cells (13,14). Cortactin undergoes phosphorylation on Tyr-421 in fibroblasts during cell migration, and this has been implicated in the activation of cortactin (14).…”

mentioning

confidence: 99%

“…Cortactin undergoes phosphorylation on Tyr-421 in fibroblasts during cell migration, and this has been implicated in the activation of cortactin (14). Cortactin may regulate actin polymerization by affecting the functional state of neuronal Wiskott-Aldrich syndrome protein, the Arp2/3 complex, and Nck in nonmuscle cells such as mouse embryonic fibroblasts and mouse 3T3 cells (13,15).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Association of Cortactin with Profilin-1 Is Critical for Smooth Muscle Contraction

Wang

Cleary

Wang

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Profilin-1 (Pfn-1) regulates actin dynamics and contraction in smooth muscle. Results: Contractile activation increases the association of cortactin with Pfn-1 via c-Abl, which controls actin dynamics and contraction. Conclusion:The coupling of cortactin with Pfn-1 regulated by c-Abl is critical for actin polymerization and contraction. Significance: The c-Abl-mediated cortactin/Pfn-1 interaction is a novel mechanism for the regulation of smooth muscle contraction.

show abstract

Cortactin: The Gray Eminence of the Cytoskeleton

Cited by 165 publications

References 101 publications

How distinct Arp2/3 complex variants regulate actin filament assembly

How distinct Arp2/3 complex variants regulate actin filament assembly

An essential role for cortactin in the modulation of the potassium channel Kv1.2

The Association of Cortactin with Profilin-1 Is Critical for Smooth Muscle Contraction

Contact Info

Product

Resources

About