Mutant Profilin Suppresses Mutant Actin-dependent Mitochondrial Phenotype in Saccharomyces cerevisiae

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

doi:10.1074/jbc.m110.217661

Cited by 6 publications

(10 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mutant actin bound much more tightly to profilin than did the WT actin, a significant result because the profilin binding site is distant from the site of the mutation on the actin surface. Such allostery is consistent with earlier findings about actin based on results with HD exchange experiments (11). Based on the entirety of this work, one can infer that mutation-induced effects on actin filament assembly and stability could either interfere with the proper construction of the smooth muscle contractile apparatus or the filament's ability to withstand myosin force exerted during contraction.…”

supporting

confidence: 79%

Mutant vascular actin is a TAAD misbehaving

Rubenstein¹,

Wen²

2015

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

Self Cite

View full text Add to dashboard Cite

supporting

confidence: 79%

Mutant vascular actin is a TAAD misbehaving

Rubenstein¹,

Wen²

2015

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

Self Cite

View full text Add to dashboard Cite

“…We assessed the effects of formin on actin polymerization using the C-terminal fragment of the yeast formin, Bni1, which contains the FH1 and FH2 domains (38). This Bni1 fragment has been previously shown to cause a concentration dependent increase in the nucleation rate of wild type actin with no observable change in final extent of polymerization (39).…”

Section: Effect Of Mutations On Cytoskeletal Morphology and Cellmentioning

confidence: 99%

Thoracic Aortic Aneurysm (TAAD)-causing Mutation in Actin Affects Formin Regulation of Polymerization

Malloy

Wen

Pierick

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background:The biochemical mechanisms underlying ␣-smooth muscle actin-mediated vascular disease are unknown. Results: The R256H mutation in actin alters polymerization kinetics and causes misregulation by the nucleation factor, formin. Conclusion: Mutation-based changes in conformation affect filament stability and regulation of polymerization. Significance: The Arg-256 residue stabilizes the actin helix and maintains filament conformation required for formin regulation.

show abstract

Section: Use Of Mutant Yeast Actin To Delve Into Actin's Basic Propermentioning

confidence: 99%

“…Subsequent work focused on how actin interacted with other actin binding proteins such as cofilin [Du and Frieden, 1998;Orlova et al, 2004;Bobkov et al, 2002Bobkov et al, , 2004Bobkov et al, , 2006Kudryashov et al, 2006;Benchaar et al, 2007;Grintsevich et al, 2008;Shvetsov et al, 2008;McCullough et al, 2011], profilin [Magdolen et al, 1993;Eads et al, 1998;Wen et al, 2008Wen et al, , 2011, formin [Wen and Rubenstein, 2009;Malloy et al, 2012;Wen et al, 2013], and Arp2/3 complex Kruth and Rubenstein, 2012] and how these controlled actin behavior. Most of the mutations used in these studies were not among those created by Wertman, since they did not meet the criterion of being in charge residue clusters.…”

Section: Budding Yeast As An Expression System For Mutant Actinsmentioning

confidence: 99%

“…1). Mutations in this loop at residues 167, 169, and 170 were shown to affect the binding of the adenine nucleotide in the interdomain cleft [Kudryashov et al, 2010;Wen et al, 2011], and profilin binding to this loop resulted in propagated conformational changes through the actin as demonstrated by differences in hydrogen/deuterium mass spectroscopy studies .The original Holmes actin filament model suggested that a highly hydrophobic loop between subdomains 3 and 4, termed the hydrophobic plug, extended from the actin subunit during polymerization to insert into a hydrophobic pocket at the interface of two neighboring subunits in the apposing strand. It was hypothesized that this would provide filament stability [Holmes et al, 1990].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Insights into the effects of disease‐causing mutations in human actins

Rubenstein

Wen

2014

Cytoskeleton

Self Cite

View full text Add to dashboard Cite

Mutations in all six actins in humans have now been shown to cause diseases. However, a number of factors have made it difficult to gain insight into how the changes in actin functions brought about by these pathogenic mutations result in the disease phenotype. These include the presence of multiple actins in the same cell, limited accessibility to pure mutant material, and complexities associated with the structures and their component cells that manifest the diseases. To try to circumvent these difficulties, investigators have turned to the use of model systems. This review describes these various approaches, the initial results obtained using them, and the insight they have provided into allosteric mechanisms that govern actin function. Although results so far have not explained a particular disease phenotype at the molecular level, they have provided valuable insight into actin function at the mechanistic level which can be utilized in the future to delineate the molecular bases of these different actinopathies. Key Words: actin; allostery; disease; mutation; isoforms Introduction A ctin mutations can cause human disease. However, little is known concerning the mechanisms by which these mutations lead to the disease phenotypes they produce. The goal of this review is to describe the general properties of actin, the diseases associated with mutations in actin, methodologies that might be employed to achieve a mechanistic understanding of actin based disease and efforts that have been made toward this goal. Properties of G-and F-ActinA discussion of the effects of pathogenic mutations on actin function requires a basic understanding of actin structure and its solution properties. Actin is an abundant 42 kD monomeric protein, found in virtually all eukaryotic cells, that can cycle between either a monomeric (G-actin) or polymeric (F-actin) state. It plays both contractile and structural roles in the cytoplasm, and recent studies have documented that actin in the nucleus acts as a promoter of transcription or as a member of a number of chromatin remodeling complexes Philimonenko et al., 2004;Miyamoto and Gurdon, 2011; Miyamoto et al., 2011a,b;Weston et al., 2012].G-actin is a clam-shaped protein with two domains, the inner and outer domains ( Fig. 1), connected by a hinge region, and separated by a deep cleft. Outer (subdomains 1 and 2) and inner (subdomains 3 and 4) refer to their position in the actin filament. The N and C-termini reside on opposite faces of the protein in subdomain 1. An adenine nucleotide binds deep within the inter-domain cleft, held in place by a divalent cation, and imparts stability to the protein and the filament. This latter role depends on its ability to cycle between the ATP and ADP state by virtue of a polymerization-dependent ATPase activity [Carlier et al., 1987;Korn et al., 1987]. F-actin is a polar structure with pointed (2) and barbed (1) ends referring to the arrowhead pattern formed when myosin S1 binds to F-actin in the absence of ATP [Craig et al., 1985]. The polarity of th...

show abstract

Mutant Profilin Suppresses Mutant Actin-dependent Mitochondrial Phenotype in Saccharomyces cerevisiae

Cited by 6 publications

References 56 publications

Mutant vascular actin is a TAAD misbehaving

Mutant vascular actin is a TAAD misbehaving

Thoracic Aortic Aneurysm (TAAD)-causing Mutation in Actin Affects Formin Regulation of Polymerization

Insights into the effects of disease‐causing mutations in human actins

Contact Info

Product

Resources

About