The UNC-45 Myosin Chaperone

Lee, Chi F.; Melkani, Girish C.; Bernstein, Sanford I.

doi:10.1016/b978-0-12-800177-6.00004-9

Cited by 61 publications

(38 citation statements)

References 69 publications

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“…3). The structure of unc45b protein of grass carp was accordance with that of zebrafish Etard et al 2007;Wohlgemuth et al 2007), and with the UNC-45 protein of C. elegans (Venolia et al 1999;Lee et al 2014) and Drosophila (Lee et al 2011;Lee et al 2014). Those results indicated that the unc45b protein in animals is critical for myosin stability and function.…”

Section: Discussionsupporting

confidence: 75%

“…The predicted secondary and tertiary structure of unc45b protein of grass carp has a-helix and loops, which were similar to the protein of human, zebrafish and channel catfish, C. elegans (Venolia et al 1999;Lee et al 2014) and Drosophila (Lee et al 2011;Lee et al 2014). This indicated that unc45b protein in different species had high conservation and showed important biological functions such as gene regulation and molecular recognition.…”

Section: Discussionmentioning

confidence: 96%

“…In addition, a function domain in the middle of the protein is still unknown . Differing from the UCS protein of fungi and UNC-45 protein of invertebrates such as C.elegans (Caenorhabditis elegans) Landsverk et al 2007), and Drosophila melanogaster (Lee et al 2011;Lee et al 2014), the Unc45 protein of vertebrates such as human (Hubbers et al 2007;Janiesch et al 2007), mouse , zebrafish (Etard et al 2007) and fugu has two subtypes, unc45a and unc45b. As the most important molecular chaperone in myofibril formation of vertebrate, unc45b plays an essential role in folding and assembly of skeletal and cardiac muscle sarcomere (Comyn and Pilgrim 2012).…”

Section: Introductionmentioning

confidence: 99%

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Cloning, molecular characterization, and expression analysis of the unc45 myosin chaperone b(unc45b)gene of grass carp (Ctenopharyngodon idellus)

Guo

Pan

et al. 2016

J Muscle Res Cell Motil

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Unc45 myosin chaperone b(unc45b)gene is a molecular chaperone that mediates the folding, assembly and accumulation of thick-filament myosin in the formation of sarcomere, which plays an important role in the development of striated muscle and the stability of sarcomere. In this study, the complete cDNA sequence of unc45b gene of grass carp was obtained by rapid amplification of cDNA ends (RACE), and the characteristics of the unc45b protein predicted from gene sequence was analyzed by bioinformatics methods. The differential expression pattern in tissues was also detected by quantitative real-time PCR. The results showed that the full-length of unc45b gene of grass carp is 3163 bp, which contains a 60 bp 5'UTR, a 298 bp 3'UTR, and a 2865 bp open reading frame (ORF) encoding a 934 amino acid peptide. The deduced unc45b protein exhibits a homology of 92, 86, 86 % with the protein of zebrafish (Danio rerio), channel catfish (Ietalurus punctatus) and tilapia (Oreochromis niloticus) respectively, and the protein contains UCS myosin head binding domain and TPR peptide repeat domain. The protein is a hydrophilic and non-secretory protein with a molecular mass and isoeletronic point of 103,699.8 and 7.39 Da. The structural elements of the protein includes α-helixes and loops, and the unc45b gene highly expresses in skeletal muscle and heart in grass carp. This study laid a foundation for further research in explaining the myofibril accumulation in crisped grass carp.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Cloning, molecular characterization, and expression analysis of the unc45 myosin chaperone b(unc45b)gene of grass carp (Ctenopharyngodon idellus)

Guo

Pan

et al. 2016

J Muscle Res Cell Motil

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“…Compared to other tissues, differentiated striated muscle expresses a considerably different complement of molecular chaperones (28,34,(48)(49)(50), presumably to meet its highly specific needs during the final stages of differentiation and for function and tissue homeostasis. For the Hsp90 ensemble, the remodeling is substantial.…”

Section: Discussionmentioning

confidence: 99%

A Remodeled Hsp90 Molecular Chaperone Ensemble with the Novel Cochaperone Aarsd1 Is Required for Muscle Differentiation

Echeverria

Briand

Picard

2016

Molecular and Cellular Biology

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Hsp90 is the ATP-consuming core component of a very abundant molecular chaperone machine that handles a substantial portion of the cytosolic proteome. Rather than one machine, it is in fact an ensemble of molecular machines, since most mammalian cells express two cytosolic isoforms of Hsp90 and a subset of up to 40 to 50 cochaperones and regulate their interactions and functions by a variety of posttranslational modifications. We demonstrate that the Hsp90 ensemble is fundamentally remodeled during muscle differentiation and that this remodeling is not just a consequence of muscle differentiation but possibly one of the drivers to accompany and to match the vast proteomic changes associated with this process. As myoblasts differentiate into myotubes, Hsp90␣ disappears and only Hsp90␤ remains, which is the only isoform capable of interacting with the novel musclespecific Hsp90 cochaperone Aarsd1L. Artificially maintaining Hsp90␣ or knocking down Aarsd1L expression interferes with the differentiation of C2C12 myotubes. During muscle differentiation, Aarsd1L replaces the more ubiquitous cochaperone p23 and in doing so dampens the activity of the glucocorticoid receptor, one of the Hsp90 clients relevant to muscle functions. This cochaperone switch protects muscle cells against the inhibitory effects of glucocorticoids and may contribute to preventing muscle wasting induced by excess glucocorticoids. H sp90 is a highly abundant molecular chaperone, including in nonstressed cells, which is required for the maturation, stability, activity, and/or degradation of a substantial portion of the proteome (1-5) (for a regularly updated list of Hsp90 interactors, see http://www.picard.ch/downloads/Hsp90interactors.pdf). To its clients, the Hsp90 dimer offers a moving platform whose complex choreography involves ATP hydrolysis, huge conformational changes, and dynamic interactions with a large cohort of cochaperones (3, 6-11). The cochaperones regulate and are part of the Hsp90 cycle (3,(8)(9)(10)(11), and some may act as client specificity factors (12, 13). With 40 to 50 cochaperones, far more have been reported (see http://www.picard.ch/downloads/Hsp90facts.pdf) than the ones that have been extensively characterized as interacting with Hsp90 as part of the core cycle. Moreover, Hsp90 and cochaperones are extensively regulated by posttranslational modifications (see, for example, references 14-17), and Hsp90 is present in excess over any individual cochaperone. Hence, the Hsp90 molecular chaperone machine constitutes in fact an ensemble of complexes. These complexes dynamically interchange and are fashioned by the cell specificity of signaling and cochaperone expression patterns.One of the most extensively characterized components of the Hsp90 core machinery is the cochaperone p23 (18-20), encoded by the PTGES3 gene in mammals. This small acidic protein binds and stabilizes the ATP-bound state of Hsp90 (19-23). p23 binding, which is disrupted by Hsp90 inhibitors competing with ATP and by hyperacetylation of Hsp90, promotes a ...

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“…UNC-45A is a highly conserved member of the UCS (UNC-45/Cro1/She4p) protein family, which plays a crucial role in chaperone motor protein assembly (18, 19). Our group and others have recently shown that UNC-45A interacts with and affects the folding and stability of myosins including NMIIA via direct binding with myosin heads (19).…”

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confidence: 99%

UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion

Iizuka

Cichocki

Sieben

et al. 2015

The Journal of Immunology

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NK cell’s killing is a tightly regulated process under the control of specific cytoskeletal proteins. This includes Wiskott-Aldrich-Syndrome protein, Wiskott-Aldrich-Syndrome protein-interacting protein, cofilin, Munc13-4, and nonmuscle myosin IIA (NMIIA). These proteins play a key role in controlling NK-mediated cytotoxicity either via regulating the attachment of lytic granules to the actin-based cytoskeleton or via promoting the cytoskeletal reorganization that is requisite for lytic granule release. UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins that act as chaperones for both conventional and nonconventional myosin. Although we and others have shown that in lower organisms and in mammalian cells NMIIA-associated functions, such as cytokinesis, cell motility, and organelle trafficking, are dependent upon the presence of UNC-45A, its role in NK-mediated functions is largely unknown. In this article, we describe UNC-45A as a key regulator of NK-mediated cell toxicity. Specifically we show that, in human NK cells, UNC-45A localize at the NK cell immunological synapse of activated NK cells and is part of the multiprotein complex formed during NK cell activation. Furthermore, we show that UNC-45A is disposable for NK cell immunological synapse formation and lytic granules reorientation but crucial for lytic granule exocytosis. Lastly, loss of UNC-45A leads to reduced NMIIA binding to actin, suggesting that UNC-45A is a crucial component in regulating human NK cell cytoskeletal dynamics via promoting the formation of actomyosin complexes.

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The UNC-45 Myosin Chaperone

Cited by 61 publications

References 69 publications

Cloning, molecular characterization, and expression analysis of the unc45 myosin chaperone b(unc45b)gene of grass carp (Ctenopharyngodon idellus)

Cloning, molecular characterization, and expression analysis of the unc45 myosin chaperone b(unc45b)gene of grass carp (Ctenopharyngodon idellus)

A Remodeled Hsp90 Molecular Chaperone Ensemble with the Novel Cochaperone Aarsd1 Is Required for Muscle Differentiation

UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion

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