Phosphoinositides differentially regulate α-actinin flexibility and function

Anne Marie Corgan, Coreyayne Singleton, Cynthia B. Santoso, Jeffrey A. Greenwood

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


α-Actinin is a cell-adhesion and cytoskeletal protein that bundles actin microfilaments and links these filaments directly to integrin-adhesion receptors. Phosphoinositides bind to and regulate the interaction of α-actinin with actin filaments and integrin receptors. In the present study, we demonstrate that PtdIns(3,4,5)P3 inhibits and disrupts α-actinin-bundling activity, whereas PtdIns(4,5)P2 can only inhibit activity. In addition, a protease-sensitivity assay was developed to examine the flexibility of the linker region between the actin-binding domain and the spectrin repeats of α-actinin. Both phosphoinositides influenced the extent of proteolysis and the cleavage sites. PtdIns(4,5)P2 binding decreased the proteolysis of α-actinin, suggesting a role in stabilizing the structure of the protein. In contrast, PtdIns(SAS)P3 binding enhanced α-actinin proteolysis, indicating an increase in the flexibility of the protein. Furthermore, phosphoinositide binding influenced the proteolysis of the N- and C-terminal domains of α-actinin, indicating regulation of structure within both domains. These results support the hypothesis that PtdIns(4,5)P2 and PtdIns(SAS)P3 differentially regulate α-actinin function by modulating the structure and flexibility of the protein.

Original languageEnglish (US)
Pages (from-to)1067-1072
Number of pages6
JournalBiochemical Journal
Issue number3
StatePublished - Mar 15 2004
Externally publishedYes


  • Actin bundling
  • Cytoskeleton
  • Focal adhesion
  • Phosphoinositide
  • Protein flexibility
  • α-actinin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Phosphoinositides differentially regulate α-actinin flexibility and function'. Together they form a unique fingerprint.

Cite this