共查询到20条相似文献,搜索用时 15 毫秒
1.
Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue 总被引:5,自引:0,他引:5
The dystrophin glycoprotein complex (DGC) is a multimeric protein assembly associated with either the X-linked cytoskeletal
protein dystrophin or its autosomal homologue utrophin. In striated muscle cells, the DGC links the extracellular matrix to
the actin cytoskeleton and mediates three major functions: structural stability of the plasma membrane, ion homeostasis, and
transmembrane signaling. Mutations affecting the DGC underlie major forms of congenital muscle dystrophies. The DGC is prominent
also in the central and peripheral nervous system and in tissues with a secretory function or which form barriers between
functional compartments, such as the blood-brain barrier, choroid plexus, or kidney. A considerable molecular heterogeneity
arises from cell-specific expression of its constituent proteins, notably short C-terminal isoforms of dystrophin. Experimentally,
the generation of mice carrying targeted gene deletions affecting the DGC has clarified the interdependence of DGC proteins
for assembly of the complex and revealed its importance for brain development and regulation of the ’milieu intérieur. Here,
we focus on recent studies of the DGC in brain, blood-brain barrier and choroid plexus, retina, and kidney and discuss the
role of dystrophin isoforms and utrophin for assembly of the complex in these tissues.
Received 4 October 2005; received after revision 14 March 2006; accepted 5 April 2006 相似文献
2.
Hiroshi Ueno Kano Suzuki Takeshi Murata 《Cellular and molecular life sciences : CMLS》2018,75(10):1789-1802
Rotary ATPases are unique rotary molecular motors that function as energy conversion machines. Among all known rotary ATPases, F1-ATPase is the best characterized rotary molecular motor. There are many high-resolution crystal structures and the rotation dynamics have been investigated in detail by extensive single-molecule studies. In contrast, knowledge on the structure and rotation dynamics of V1-ATPase, another rotary ATPase, has been limited. However, recent high-resolution structural studies and single-molecule studies on V1-ATPase have provided new insights on how the catalytic sites in this molecular motor change its conformation during rotation driven by ATP hydrolysis. In this review, we summarize recent information on the structural features and rotary dynamics of V1-ATPase revealed from structural and single-molecule approaches and discuss the possible chemomechanical coupling scheme of V1-ATPase with a focus on differences between rotary molecular motors. 相似文献
3.
Kostyukova AS 《Cellular and molecular life sciences : CMLS》2008,65(4):563-569
The tropomodulins are a family of proteins that cap the slow-growing (pointed) end of actin filaments and require tropomyosin
for optimal function. Tropomodulin is an elongated molecule with a molecular mass of about 40 kDa. The C-terminal half of
tropomodulin contains one compact cooperatively melting domain, whereas the N-terminal half has no cooperatively melting structure.
The N-terminal half of tropomodulin contains two tropomysin-binding sites and a tropomyosin-dependent actin-binding site,
the tropomyosin-independent actin-binding site being located at the C terminus. One tropomodulin molecule binds two tropomyosin
molecules, and thus one molecule of tropomodulin is necessary and sufficient for capping at the pointed end. Tropomyosin/tropomodulin
interactions are isoform specific. Differences in tropomyosin affinity for the two binding sites in tropomodulin may regulate
its correct positioning at the pointed end as well as effectiveness of capping the actin filament.
Received 30 July 2007; received after revision 2 October 2007; accepted 10 October 2007 相似文献
4.
Doucey MA Bender FC Hess D Hofsteenge J Bron C 《Cellular and molecular life sciences : CMLS》2006,63(7-8):939-948
We report that caveolin-1, one of the major structural protein of caveolae, interacts with TCP-1, a hetero-oligomeric chaperone
complex present in all eukaryotic cells that contributes mainly to the folding of actin and tubulin. The caveolin-TCP-1 interaction
entails the first 32 amino acids of the N-terminal segment of caveolin. Our data show that caveolin-1 expression is needed
for the induction of TCP-1 actin folding function in response to insulin stimulation. Caveolin-1 phosphorylation at tyrosine
residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by which
caveolin-1 modulates TCP-1 activity is indirect and involves the cytoskeleton linker filamin. Filamin is known to bind caveolin-1
and to function as a negative regulator of insulin-mediated signaling. Our data support the notion that the caveolin-filamin
interaction contributes to restore insulin-mediated phosphorylation of caveolin, thus allowing the release of active TCP-1.
Received 17 November 2005; received after revision 1 December 2005; accepted 17 February 2006 相似文献
5.
H. Riezman A. Munn M. I. Geli L. Hicke 《Cellular and molecular life sciences : CMLS》1996,52(12):1033-1041
Endocytosis is a general term that is used to describe the internalization of external and plasma membrane molecules into the cell interior. In fact, several different mechanisms exist for the internalization step of this process. In this review we emphasize the work on the actin-dependent pathways, in particular in the yeastSaccharomyces cerevisiae, because several components of the molecular machinery are identified. In this yeast, the analysis of endocytosis in various mutants reveals a requirement for actin, calmodulin, a type I myosin, as well as a number of other proteins that affect actin dynamics. Some of these proteins have homology to proteins in animal cells that are believed to be involved in endocytosis. In addition, the demonstration that ubiquitination of some cell surface molecules is required for their efficient internalization is described. We compare the actin, myosin and ubiquitin requirements for endocytosis with recent results found studying these processes usingDictyostelium discoideum and animal cells. 相似文献
6.
Au Y 《Cellular and molecular life sciences : CMLS》2004,61(24):3016-3033
Muscle ultrastructure is characterised by a complex arrangement of many protein-protein interactions. The sarcomere is the basic repeating unit of muscle, formed by two transverse filament systems: the thick and thin filaments. While actin and myosin are the main contractile elements of the sarcomere, other proteins act as scaffolds, control ultrastructure composition, regulate muscle contraction, and transmit tension between sarcomeres and hence to the whole myofibril. Elucidation of the structures of muscle proteins by X-ray crystallography and nuclear magnetic resonance spectroscopy has been essential in understanding muscle contraction, enabling us to relate biological to structural information. These structures reveal how components of the muscle interact, how different factors influence conformational changes within these proteins, and how mutant muscle proteins may interfere with the regulatory fine-tuning of the contractile machinery, hence leading to disease in some cases. Here, structures solved within the sarcomere have been reviewed in order to put the numerous components into context.Received 28 June 2004; received after revision 25 July 2004; accepted 28 July 2004 相似文献
7.
Hearing molecules: contributions from genetic deafness 总被引:1,自引:0,他引:1
Considerable progress has been made over the past decade identifying many genes associated with deafness. With the identification
of these hereditary deafness genes and the proteins they encode, molecular elements of basic hearing mechanisms emerge. As
functional studies of these molecular elements become available, we can put together the pieces of the puzzle and begin to
reach an understanding of the molecular mechanisms of hearing. The goal of this review is to discuss studies over the past
decade that address the function of the proteins implicated in genetic deafness and to place them in the context of basic
molecular mechanisms in hearing. The first part of this review highlights structural and functional features of the cochlea
and auditory nerve. This background will provide a context for the second part, which addresses the molecular mechanisms underlying
cochlear function as elucidated by genetic causes of deafness.
Received 20 September 2006; received after revision 24 October 2006; accepted 5 December 2006 相似文献
8.
Interleukin (IL)-1 is a proinflammatory cytokine with important roles in innate immunity, as well as in normal tissue homeostasis.
Interestingly, recent studies have also shown IL-1 to function in the dynamics of the actin cytoskeleton and cell junctions.
For example, treatment of different epithelia with IL-1α often results in the restructuring of the actin network and cell
junctions, thereby leading to junction disassembly. In this review, we highlight new and interesting findings that show IL-1
to be a critical player of restructuring events in the seminiferous epithelium of the testis during spermatogenesis. 相似文献
9.
Natalie Porat-Shliom Oleg Milberg Andrius Masedunskas Roberto Weigert 《Cellular and molecular life sciences : CMLS》2013,70(12):2099-2121
Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e., secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane, and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. 相似文献
10.
Yun Hyun Huh So Hee Kim Kyoung-Hwun Chung Sena Oh Min-Sung Kwon Hyun-Woo Choi Sangmyung Rhee Je-Hwang Ryu Zee Yong Park Chang-Duk Jun Woo Keun Song 《Cellular and molecular life sciences : CMLS》2013,70(24):4841-4854
Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells. 相似文献
11.
Jensen MR Hass MA Hansen DF Led JJ 《Cellular and molecular life sciences : CMLS》2007,64(9):1085-1104
Metal ions play a key role for the function of many proteins. The interaction of the metal ion with the protein and its involvement
in the function of the protein vary widely. In some proteins, the metal ion is bound tightly to the ligand residues and may
be the key player in the function of the protein, as in the case of blue copper proteins. In other proteins, the metal ion
is bound only temporarily and loosely to the protein, as in the case of some metalloenzymes and other proteins where the metal
ion acts as a cofactor necessary for the function of the protein. Such proteins are often known as metal ion-activated proteins.
The review focuses on recent nuclear magnetic resonance (NMR) studies of a series of metal-dependent proteins and the characterization
of the metal-binding sites. In particular, we focus on NMR techniques for studying metal binding to proteins such as chemical
shift mapping, paramagnetic NMR and changes in backbone dynamics upon metal binding.
Received 12 October 2006; received after revision 30 November 2006; accepted 5 February 2007 相似文献
12.
Cowan-Jacob SW 《Cellular and molecular life sciences : CMLS》2006,63(22):2608-2625
Our current understanding of the structure, mechanism of action and modes of regulation of the protein tyrosine kinase family
owes a great deal to structural biology. Structures are now available for more than 20 different tyrosine kinase domains,
many of these in multiple conformational states. They form the basis for the design of experiments to further investigate
the role of different structural elements in the normal function and regulation of the protein and in the pathogenesis of
many human diseases. Once thought to be too similar to be specifically inhibited by a small molecule, structural differences
between kinases allow the design of compounds which inhibit only an acceptable few. This review gives a general overview of
protein tyrosine kinase structural biology, including a discussion of the strengths and limitations of the investigative methods
involved.
Received 2 May 2006; received after revision 21 June 2006; accepted 9 August 2006 相似文献
13.
Sarramegn V Muller I Milon A Talmont F 《Cellular and molecular life sciences : CMLS》2006,63(10):1149-1164
G protein-coupled receptors (GPCRS) represent a class of integral membrane proteins involved in many biological processes
and pathologies. Fifty percent of all modern drugs and almost 25% of the top 200 bestselling drugs are estimated to target
GPCRs. Despite these crucial biological implications, very little is known, at atomic resolution, about the detailed molecular
mechanisms by which these membrane proteins are able to recognize their extra-cellular stimuli and transmit the associated
messages. Obviously, our understanding of GPCR functioning would be greatly facilitated by the availability of high-resolution
three-dimensional (3D) structural data. However, expression, solubilization and purification of these membrane proteins are
not easy to achieve, and at present, only one 3D structure has been determined, that of bovine rhodopsin. This review presents
and compares the different successful strategies which have been applied to solubilize and purify recombinant GPCRs in the
perspective of structural biology experiments.
Received 21 November 2005; received after revision 20 January 2006; accepted 2 February 2006
An erratum to this article is available at . 相似文献
14.
Vincent E Saxton J Baker-Glenn C Moal I Hirst JD Pattenden G Shaw PE 《Cellular and molecular life sciences : CMLS》2007,64(4):487-497
Several marine macrolide toxins act as potent and specific actin-severing molecules. Recent elucidation of their stereochemistries
and modes of interaction with actin has allowed the syntheses of bioactive analogues. Here we used synthetic analogues in
a structure-function analysis of ulapualide A, a trisoxazole-based macrolide. Ulapualide A harboured potent actin-depolymerising
activity both in cells and in vitro. Its synthetic diastereoisomer was three orders of magnitude less active than the natural toxin and synthetic macrolide fragments
lacked actin-capping/ severing activity altogether. Modulation of serum response factor (SRF)-dependent gene expression, as
described for other actin-binding toxins, was also examined. Specific changes in response to ulapualide A were not observed,
primarily due to its profound effects on cytoskeletal integrity and cell adhesion. Several synthetic fragments of ulapualide
A also had no effect on SRF-dependent gene expression. However, inhibition was observed with a molecule corresponding to the
extended aliphatic side chain of halichondramide, a structurally related macrolide. These findings indicate that side-chain
derivatives of trisoxazole-based macrolides may serve to uncouple gene-regulatory events from actin dynamics.
E. Vincent and J. Saxton: These two authors contributed equally
Received 27 September 2006; received after revision 30 November 2006; accepted 8 January 2007 相似文献
15.
ROPs in the spotlight of plant signal transduction 总被引:7,自引:0,他引:7
Berken A 《Cellular and molecular life sciences : CMLS》2006,63(21):2446-2459
Small guanine nucleotide binding proteins of the Rho family called ROP play a crucial role as regulators of signal transduction
in plants. They participate in pathways that influence growth and development, and the adaptation of plants to various environmental
situations. As members of the Ras superfamily, ROPs function as molecular switches cycling between a GDP-bound ‘off’ and a
GTP-bound ‘on’ state in a strictly regulated manner. Latest research provided fascinating new insights into ROP regulation
by novel guanine nucleotide exchange factors, unconventional GTPase activating proteins, and guanine nucleotide dissociation
inhibitors, which apparently organize localized ROP activation. Important progress has also been made concerning signaling
components upstream and downstream of the ROP cycle involving receptor-like serine/threonine kinases and effectors that can
manipulate cytoskeletal dynamics, intracellular calcium levels, H2O2 production and further cellular targets. This review outlines the fast developing knowledge on ROP GTPases highlighting their
specific features, regulation and roles in a cellular signaling context.
Received 28 April 2006; received after revision 2 June 2006; accepted 29 June 2006 相似文献
16.
The function of apolipoproteins L 总被引:1,自引:0,他引:1
The function of the proteins of the apolipoprotein L (apoL) family is largely unknown. These proteins are classically thought
to be involved in lipid transport and metabolism, mainly due to the initial discovery that a secreted member of the family,
apoL-I, is associated with high-density lipoprotein particles. However, the other members of the family are believed to be
intracellular. The recent unravelling of the mechanism by which apoL-I kills African trypanosomes, as well as the increasing
evidence for modulation of apoL expression in various pathological processes, provides new insights about the functions of
these proteins. ApoLs share structural and functional similarities with proteins of the Bcl-2 family. Based on the activity
of apoL-I in trypanosomes and the comparison with Bcl-2 proteins, we propose that apoLs could function as ion channels of
intracellular membranes and be involved in mechanisms triggering programmed cell death.
Received 28 February 2006; received after revision 18 May 2006; accepted 2 June 2006 相似文献
17.
Biological membrane fusion is driven by different types of molecular fusion machines. Most of these proteins are membrane-anchored
by single transmembrane domains. SNARE proteins are essential for intracellular membrane fusion along the secretory and endocytic
pathway, while various viral fusogens mediate infection of eukaryotic cells by enveloped viruses. Although both types of fusion
proteins are evolutionarily quite distant from each other, they do share a number of structural and functional features. Their
transmembrane domains are now known to be critical for the fusion reaction. We discuss at which stages they might contribute
to bilayer mixing.
Received 5 October 2006; received after revision 14 November 2006; accepted 8 January 2007 相似文献
18.
Garima Jaipuria Tina Ukmar-Godec Markus Zweckstetter 《Cellular and molecular life sciences : CMLS》2018,75(12):2137-2151
Experimental evidence for a direct role of lipids in determining the structure, dynamics, and function of membrane proteins leads to the term ‘functional lipids’. In particular, the sterol molecule cholesterol modulates the activity of many membrane proteins. The precise nature of cholesterol-binding sites and the consequences of modulation of local membrane micro-viscosity by cholesterol, however, is often unknown. Here, we review the current knowledge of the interaction of cholesterol with transmembrane proteins, with a special focus on structural aspects of the interaction derived from nuclear magnetic resonance approaches. We highlight examples of the importance of cholesterol modulation of membrane protein function, discuss the specificity of cholesterol binding, and review the proposed binding motifs from a molecular perspective. We conclude with a short perspective on what could be future trends in research efforts targeted towards a better understanding of cholesterol/membrane protein interactions. 相似文献
19.
The adaptive significance of sexuality 总被引:2,自引:0,他引:2
H J Bremermann 《Experientia》1985,41(10):1245-1254
A theory of sexuality and polymorphism is proposed in which diversity at the molecular level is the adaptive response of multicellular organisms to the challenge of microparasites that have smaller genomes, shorter generation times and which can evolve more quickly than their hosts. The theory has implications for genetically homogenized crops and other cultivated plants as well as for immunology. A different function of sexuality is proposed for microorganisms that reproduce both asexually and sexually. Several possible experimental tests are discussed. Mathematical modelling techniques are outlined qualitatively and compared with game-theoretical methods which may be interpreted as simplifications of population dynamics of polymorphic host-parasite populations are referenced. 相似文献
20.
Actin polymerization machinery: the finish line of signaling networks, the starting point of cellular movement 总被引:9,自引:0,他引:9
Disanza A Steffen A Hertzog M Frittoli E Rottner K Scita G 《Cellular and molecular life sciences : CMLS》2005,62(9):955-970
Dynamic assembly of actin filaments generates the forces supporting cell motility. Several recent biochemical and genetic studies have revealed a plethora of different actin binding proteins whose coordinated activity regulates the turnover of actin filaments, thus controlling a variety of actin-based processes, including cell migration. Additionally, emerging evidence is highlighting a scenario whereby the same basic set of actin regulatory proteins is also the convergent node of different signaling pathways emanating from extracellular stimuli, like those from receptor tyrosine kinases. Here, we will focus on the molecular mechanisms of how the machinery of actin polymerization functions and is regulated, in a signaling-dependent mode, to generate site-directed actin assembly leading to cell motility.These authors contributed equally to this work.Received 26 October 2004; received after revision 27 December 2004; accepted 6 January 2005 Available online 09 March 2005 相似文献