Mutant profilin suppresses mutant actin-dependent mitochondrial phenotype in Saccharomyces cerevisiae

Kuo Kuang Wen, Melissa McKane, Ema Stokasimov, Peter A. Rubenstein

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6 Scopus citations


In the Saccharomyces cerevisiae actin-profilin interface, Ala 167 of the actin barbed end W-loop and His 372 near the C terminus form a clamp around a profilin segment containing residue Arg 81 and Tyr 79. Modeling suggests that altering steric packing in this interface regulates actin activity. An actin A167E mutation could increase interface crowding and alter actin regulation, and A167E does cause growth defects and mitochondrial dysfunction. We assessed whether a profilin Y79S mutation with its decreased mass could compensate for actin A167E crowding and rescue the mutant phenotype. Y79S profilin alone caused no growth defect in WT actin cells under standard conditions in rich medium and rescued the mitochondrial phenotype resulting from both the A167E and H372R actin mutations in vivo consistent with our model. Rescue did not result from effects of profilin on actin nucleotide exchange or direct effects of profilin on actin polymerization. Polymerization of A167E actin was less stimulated by formin Bni1 FH1-FH2 fragment than was WT actin. Addition of WT profilin to mixtures of A167E actin and formin fragment significantly altered polymerization kinetics from hyperbolic to a decidedly more sigmoidal behavior. Substitution of Y79S profilin in this system produced A167E behavior nearly identical to that of WT actin. A167E actin caused more dynamic actin cable behavior in vivo than observed with WT actin. Introduction of Y79S restored cable movement to a more normal phenotype. Our studies implicate the importance of the actin-profilin interface for formin-dependent actin and point to the involvement of formin and profilin in the maintenance of mitochondrial integrity and function.

Original languageEnglish (US)
Pages (from-to)41745-41757
Number of pages13
JournalJournal of Biological Chemistry
Issue number48
StatePublished - Dec 2 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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