Bax inhibitor 1 increases cell adhesion through actin polymerization: Involvement of calcium and actin binding

Geum Hwa Lee, Taeho Ahn, Do Sung Kim, Seoung Ju Park, Yong Chul Lee, Wan Hee Yoo, Sung Jun Jung, Jae Seong Yang, Sanguk Kim, Andras Muhlrad, Young Rok Seo, Soo Wan Chae, Hyung Ryong Kim*, Han Jung Chae

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Bax inhibitor 1 (BI-1), a transmembrane protein with Ca2+ channel-like activity, has antiapoptotic and anticancer activities. Cells overexpressing BI-1 demonstrated increased cell adhesion. Using a proteomics tool, we found that BI-1 interacted with γ-actin via leucines 221 and 225 and could control actin polymerization and cell adhesion. Among BI-1 -/- cells and cells transfected with BI-1 small interfering RNA (siRNA), levels of actin polymerization and cell adhesion were lower than those among BI-1+/+ cells and cells transfected with nonspecific siRNA. BI-1 acts as a leaky Ca2+ channel, but mutations of the actin binding sites (L221A, L225A, and L221A/L225A) did not change intra-endoplasmic reticulum Ca2+, although deleting the C-terminal motif (EKDKKKEKK) did. However, store-operated Ca2+ entry (SOCE) is activated in cells expressing BI-1 but not in cells expressing actin binding site mutants, even those with the intact C-terminal motif. Consistently, actin polymerization and cell adhesion were inhibited among all the mutant cells. Compared to BI-1 +/+ cells, BI-1-/- cells inhibited SOCE, actin polymerization, and cell adhesion. Endogenous BI-1 knockdown cells showed a similar pattern. The C-terminal peptide of BI-1 (LMMLILAMNRKDKKKEKK) polymerized actin even after the deletion of four or six charged C-terminal residues. This indicates that the actin binding site containing L221 to D231 of BI-1 is responsible for actin interaction and that the C-terminal motif has only a supporting role. The intact C-terminal peptide also bundled actin and increased cell adhesion. The results of experiments with whole recombinant BI-1 reconstituted in membranes also coincide well with the results obtained with peptides. In summary, BI-1 increased actin polymerization and cell adhesion through Ca2+ regulation and actin interaction.

Original languageEnglish
Pages (from-to)1800-1813
Number of pages14
JournalMolecular and Cellular Biology
Volume30
Issue number7
DOIs
StatePublished - Apr 2010

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