An N-terminal, 830 residues intrinsically disordered region of the cytoskeleton-regulatory protein supervillin contains Myosin II- and F-actin-binding sites

Fedechkin, Stanislav O.; Brockerman, Jacob; Luna, Elizabeth J.; Лобанов, М. Л.; Galzitskaya, Oxana V.; Smirnov, S. K.

doi:10.1080/07391102.2012.726531

Cited by 13 publications

(17 citation statements)

References 52 publications

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“…Supervillin's amino acid sequence indicates the presence of five gelsolin-like domains that correspond to G2-G6 of gelsolin, with a villin-like headpiece at its Cterminus, and a unique intrinsically disordered N-terminal domain [Fedechkin et al, In press] that contains four nuclear localization signals [Wulfkuhle et al, 1999]. Detailed domain analysis suggests that contrary to expectations, the gelsolin-like C-terminal half binds F-actin weakly, that the villin-like headpiece lacks F-actin binding altogether, and that F-actin binding and actin filament bundling activities are localized to the novel disordered Nterminal region [Wulfkuhle et al, 1999;Vardar et al, 2002;Fedechkin et al, In press]. The weak actin binding is consistent with the lack of conservation of actin-binding surfaces present in gelsolin.…”

Section: The Gelsolin Superfamilymentioning

confidence: 99%

Gelsolin: The tail of a molecular gymnast

et al. 2013

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Gelsolin superfamily members are Ca 21 -dependent, multidomain regulators of the actin cytoskeleton. Calcium binding activates gelsolin by inducing molecular gymnastics (large-scale conformational changes) that expose actin interaction surfaces by releasing a series of latches. A specialized tail latch has distinguished gelsolin within the superfamily. Active gelsolin exhibits actin filament severing and capping, and actin monomer sequestering activities. Here, we analyze a combination of sequence, structural, biophysical and biochemical data to assess whether the molecular plasticity, regulation and actinrelated properties of gelsolin are also present in other superfamily members. We conclude that all members of the superfamily will be able to transition between a compact conformation and a more open form, and that most of these open forms will interact with actin. Supervillin, which lacks the severing domain 1 and the F-actin binding-site on domain 2, is the clear exception. Eight calcium-binding sites are absolutely conserved in gelsolin, adseverin, advillin and villin, and compromised to increasing degrees in CapG, villin-like protein, supervillin and flightless I. Advillin, villin and supervillin each contain a potential tail latch, which is absent from CapG, adseverin and flightless I, and ambiguous in villin-like protein. Thus, calcium regulation will vary across the superfamily. Potential novel isoforms of the superfamily suggest complex regulation at the gene, transcript and protein levels. We review animal, clinical and cellular data that illuminate how the regulation of molecular flexibility in gelsolin-like proteins permits cells to exploit the force generated from actin polymerization to drive processes such as cell movement in health and disease. V C 2013 Wiley Periodicals, Inc.

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Section: The Gelsolin Superfamilymentioning

confidence: 99%

Gelsolin: The tail of a molecular gymnast

et al. 2013

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“…Examples include the afore‐mentioned cortactin and supervillin which belongs to the villin/gelsolin family of actin‐organizing proteins [Silacci et al, ] which also contains the members dematin and gelsolin that possess IDRs of 315 and 40 residues, respectively [Chen et al, ; Smirnov et al, ]. Supervillin has a unique, more than 800 amino acid long, intrinsically disordered N‐terminus which promotes interactions with several signaling proteins and major cytoskeletal components, including F‐actin and human nonmuscle myosin II [Chen et al, ; Crowley et al, ; Fedechkin et al, ] and it influences cytokinesis, cell motility and can promote invasive activity in tumors by formation of invadopodia or podosomes [Crowley et al, ; Weaver, ]. Invadopodia and podosomes are actin‐rich protrusions that form at sites of extracellular matrix (ECM) degradation [Weaver, ]; tumor cells forming the highly active invadopodia are particularly invasive and migratory [Weaver, ].…”

Section: Abps In Actin Filament Growth and Organizationmentioning

confidence: 99%

Intrinsic Structural Disorder in Cytoskeletal Proteins

et al. 2013

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Cytoskeleton, the internal scaffold of the cell, displays an exceptional combination of stability and dynamics. It is composed of three major filamentous networks, microfilaments (actin filaments), intermediate filaments (neurofilaments), and microtubules. Together, they ensure the physical and structural stability of the cell, whereby also mediating its large-scale structural rearrangements, motility, stress response, division, and internal transport. All three cytoskeletal systems are built upon the same basic design: they have a central repetitive scaffold assembled from folded building elements, surrounded and regulated by accessory regions/proteins that regulate its formation and mediate its countless interactions with its environment, serving to send regulatory signals to and from the cytoskeleton. Here, we elaborate on the idea that the opposing features of stability and dynamics are also manifest in the dichotomy of the structural status of its components, the core being highly structured and the accessory proteins/regions being highly disordered, and are responsible for most of the regulatory (post-translational) input promoting adaptive responses and providing dynamics necessary for each of the cytoskeletal systems. This pattern entails special consequences, in which the manifold functional advantages of structural disorder, most pronounced in regulatory and signaling functions, are all exploited by nature. (MTs), and it provides the internal scaffold (skeleton) of the cell. It can be considered as a very special organelle, which represents a unique combination of stability and dynamics, physical rigidity and flexibility, long-time persistence and rapid, cataclysmic rearrangements. By providing a special microenvironment, the cytoskeleton ensures the physical separation of cellular constituents, thus segregating and directing cellular activities. It bridges molecular (nano-m) and cellular (micro-m) distances and represent the tracks of transport of cellular constituents over large distances. It provides the locomotive force of cell migration, it drives clustering of membrane proteins, drives cell division and the formation of protrusions the cell uses for exploring its environment. Apparently it does it by a combination of a physically rigid but inherently unstable central scaffold and a flexible and rather variable outer layer of accessory proteins/regions. Due to its central importance in cell physiology, the cytoskeleton is involved in many diseases, ranging from cancer to neurodegeneration [Pajkos et al., 2012;Raychaudhuri et al., 2009;Uversky et al., 2008]. Our central theme here is that multifaceted and highly dynamic behavior is enabled by structural disorder in all three major cytoskeletal constituents, also reflecting their increasing complexity from NFs to the actin cytoskeleton (Supporting Information Table S1, Table I). Intermediate filaments (IFs) have three principal components, IF-L(ight), IF-M(edium), and IF-H(igh), all three of which form an extended coiled-coil structures, from which...

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“…Supervillin binds myosin II and F-actin with regions near the protein N-terminus (M and A1, A2, A3, respectively, in Fig 1B ) [ 19 ]. All four binding regions [ 19 , 33 ] are conserved in vertebrates ( Fig 1C ). Based on this information, we hypothesized supervillin may localize to specific actin-rich organelles in the hair cell, as it localizes to invadopodia in MDA-MB-231 metastatic breast carcinoma cells [ 34 ] or contractile rings in dividing HeLa cells [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Supervillin Is a Component of the Hair Cell’s Cuticular Plate and the Head Plates of Organ of Corti Supporting Cells

et al. 2016

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The organ of Corti has evolved a panoply of cells with extraordinary morphological specializations to harness, direct, and transduce mechanical energy into electrical signals. Among the cells with prominent apical specializations are hair cells and nearby supporting cells. At the apical surface of each hair cell is a mechanosensitive hair bundle of filamentous actin (F-actin)-based stereocilia, which insert rootlets into the F-actin meshwork of the underlying cuticular plate, a rigid organelle considered to hold the stereocilia in place. Little is known about the protein composition and development of the cuticular plate or the apicolateral specializations of organ of Corti supporting cells. We show that supervillin, an F-actin cross-linking protein, localizes to cuticular plates in hair cells of the mouse cochlea and vestibule and zebrafish sensory epithelia. Moreover, supervillin localizes near the apicolateral margins within the head plates of Deiters’ cells and outer pillar cells, and proximal to the apicolateral margins of inner phalangeal cells, adjacent to the junctions with neighboring hair cells. Overall, supervillin localization suggests this protein may shape the surface structure of the organ of Corti.

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An N-terminal, 830 residues intrinsically disordered region of the cytoskeleton-regulatory protein supervillin contains Myosin II- and F-actin-binding sites

Cited by 13 publications

References 52 publications

Gelsolin: The tail of a molecular gymnast

Gelsolin: The tail of a molecular gymnast

Intrinsic Structural Disorder in Cytoskeletal Proteins

Supervillin Is a Component of the Hair Cell’s Cuticular Plate and the Head Plates of Organ of Corti Supporting Cells

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