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1.
The molecular architecture of tight junctions has been a subject of extensive studies that have shown tight junctions to be
composed of many peripheral and integral membrane proteins. Claudins have been considered the main tight junction-forming
proteins; however, the role they play in a series of pathophysiological events, including human carcinoma development, is
only now beginning to be understood. Increasing evidence from in vitro and in vivo studies have identified the influence of claudins on tight junction structure and function, although claudins also participate
in cellular contexts other than tight junctions. The aim of this review is to summarize and discuss the conceptual framework
concerning claudins, focusing on the involvement of these proteins in epithelial cell polarity establishment, paracellular
transport control, signal transduction and tumorigenesis.
Received 5 July 2006; received after revision 29 August 2006; accepted 29 September 2006 相似文献
2.
The search for the right partner: Homologous pairing and DNA strand exchange proteins in eukaryotes 总被引:13,自引:0,他引:13
W. -D. Heyer 《Cellular and molecular life sciences : CMLS》1994,50(3):223-233
Finding the right partner is a central problem in homologous recombination. Common to all models for general recombination is a homologous pairing and DNA strand exchange step. In prokaryotes this process has mainly been studied with the RecA protein ofEscherichia coli. Two approaches have been used to find homologous pairing and DNA strand exchange proteins in eukaryotes. A biochemical approach has resulted in numerous proteins from various organisms. Almost all of these proteins are biochemically fundamentally different from RecA. The in vivo role of these proteins is largely not understood. A molecular-genetical approach has identified structural homologs to theE. coli RecA protein in the yeastSaccharomyces cerevisiae and subsequently in other organisms including other fungi, mammals, birds, and plants. The biochemistry of the eukaryotic RecA homologs is largely unsolved. For the fungal RecA homologs (S. cerevisiae RAD51, RAD55, RAD57, DMC1; Schizosaccharomyces pombe rad51; Neurospora crassa mei3) a role in homologous recombination and recombinational repair is evident. Besides recombination, homologous pairing proteins might be involved in other cellular processes like chromosome pairing or gene inactivation. 相似文献
3.
Blasig IE Winkler L Lassowski B Mueller SL Zuleger N Krause E Krause G Gast K Kolbe M Piontek J 《Cellular and molecular life sciences : CMLS》2006,63(4):505-514
Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated
the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin
was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the
same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5
also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates
self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of
occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular
loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption
that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction
assembly is supported.
Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005
†These authors contributed equally to this work. 相似文献
4.
The prokaryotic pore-forming proteins are synthesized in the cytoplasm, and are assembled in their functional form in the outer membrane. They begin to traverse the cytoplasmic membrane via the SecY/SecA export pathway, which is shared also by periplasmic proteins. The sorting signals that direct these proteins to the outer membrane could be present in the three-dimensional conformations of the proteins, but some results suggest that they may be present in short, contiguous sequences. Outer membrane proteins share a rather hydrophilic amino acid composition, and appear to be rich in beta-sheets (with the exception of lipoproteins). This observation as well as the demonstration of periplasmic export intermediates favor the secretion pathway through the periplasm, as opposed to export through fusion sites between the inner and the outer membrane, but such intermediates have not yet been observed with the wild type proteins under physiological conditions. 相似文献
5.
Kirkpatrick DT 《Cellular and molecular life sciences : CMLS》1999,55(3):437-449
Numerous proteins are involved in the nucleotide excision repair (NER) and DNA mismatch repair (MMR) pathways. The function
and specificity of these proteins during the mitotic cell cycle has been actively investigated, in large part due to the involvement
of these systems in human diseases. In contrast, comparatively little is known about their functioning during meiosis. At
least three repair pathways operate during meiosis in the yeast Saccharomyces cerevisiae to repair mismatches that occur as a consequence of heteroduplex formation in recombination. The first pathway is similar
to the one acting during postreplicative mismatch repair in mitotically dividing cells, while two pathways are responsible
for the repair of large loops during meiosis, using proteins from MMR and NER systems. Some MMR proteins also help prevent
recombination between diverged sequences during meiosis, and act late in recombination to affect the resolution of crossovers.
This review will discuss the current status of DNA mismatch repair and nucleotide excision repair proteins during meiosis,
especially in the yeast S. cerevisiae.
Received 21 September 1998; received after revision 23 November 1998; accepted 23 November 1998 相似文献
6.
DnaJ/Hsp40 (heat shock protein 40) proteins have been preserved throughout evolution and are important for protein translation,
folding, unfolding, translocation, and degradation, primarily by stimulating the ATPase activity of chaperone proteins, Hsp70s.
Because the ATP hydrolysis is essential for the activity of Hsp70s, DnaJ/Hsp40 proteins actually determine the activity of
Hsp70s by stabilizing their interaction with substrate proteins. DnaJ/Hsp40 proteins all contain the J domain through which
they bind to Hsp70s and can be categorized into three groups, depending on the presence of other domains. Six DnaJ homologs
have been identified in Escherichia coli and 22 in Saccharomyces cerevisiae. Genome-wide analysis has revealed 41 DnaJ/Hsp40 family members (or putative members) in humans. While 34 contain the typical
J domains, 7 bear partially conserved J-like domains, but are still suggested to function as DnaJ/ Hsp40 proteins. DnaJA2b,
DnaJB1b, DnaJC2, DnaJC20, and DnaJC21 are named for the first time in this review; all other human DnaJ proteins were dubbed
according to their gene names, e.g. DnaJA1 is the human protein named after its gene DNAJA1. This review highlights the progress
in studying the domains in DnaJ/Hsp40 proteins, introduces the mechanisms by which they interact with Hsp70s, and stresses
their functional diversity.
Received 27 April 2006; received after revision 5 June 2006; accepted 19 July 2006 相似文献
7.
The bacterial insertion sequence IS21 shares with many insertion sequences a two-step, reactive junction transposition pathway, for which a model is presented in this review: a reactive junction with abutted inverted repeats is first formed and subsequently integrated into the target DNA. The reactive junction occurs in IS21-IS21 tandems and IS21 minicircles. In addition, IS21 shows a unique specialization of transposition functions. By alternative translation initiation, the transposase gene codes for two products: the transposase, capable of promoting both steps of the reactive junction pathway, and the cointegrase, which only promotes the integration of reactive junctions but with higher efficiency. This review also includes a survey of the IS21 family and speculates on the possibility that other members present a similar transpositional specialization. 相似文献
8.
H. Van Dael 《Cellular and molecular life sciences : CMLS》1998,54(11):1217-1230
Protein folding is an extremely active field of research where biology, chemistry, computer science and physics meet. Although
the study of protein-folding intermediates in general and equilibrium intermediates in particular has grown considerably in
recent years, many questions regarding the conformational state and the structural features of the various partially folded
intermediate states remain unanswered. Performing kinetic measurements on proteins that have had their structures modified
by site-directed mutagenesis, the so-called protein-engineering method, is an obvious way to gain fine structural information.
In the present review, this method has been applied to a variety of proteins belonging to the lysozyme/α-lactalbumin family. Besides recombinants obtained by point mutations of individual critical residues, chimeric proteins in
which whole structural elements (10 – 25 residues) from α-lactalbumin were inserted into a human lysozyme matrix are examined. The conformational properties of the equilibrium intermediate
states are discussed together with the structural characterization of the partially unfolded states encountered in the kinetic
folding pathway.
Received 28 May 1998; received after revision 6 July 1998; accepted 6 July 1998 相似文献
9.
de Keyzer J van der Does C Driessen AJ 《Cellular and molecular life sciences : CMLS》2003,60(10):2034-2052
The major route of protein translocation in bacteria is the so-called general secretion pathway (Sec-pathway). This route has been extensively studied in Escherichia coli and other bacteria. The movement of preproteins across the cytoplasmic membrane is mediated by a multimeric membrane protein complex called translocase. The core of the translocase consists of a proteinaceous channel formed by an oligomeric assembly of the heterotrimeric membrane protein complex SecYEG and the peripheral adenosine triphosphatase (ATPase) SecA as molecular motor. Many secretory proteins utilize the molecular chaperone SecB for targeting and stabilization of the unfolded state prior to translocation, while most nascent inner membrane proteins are targeted to the translocase by the signal recognition particle and its membrane receptor. Translocation is driven by ATP hydrolysis and the proton motive force. In the last decade, genetic and biochemical studies have provided detailed insights into the mechanism of preprotein translocation. Recent crystallographic studies on SecA, SecB and the SecYEG complex now provide knowledge about the structural features of the translocation process. Here, we will discuss the mechanistic and structural basis of the translocation of proteins across and the integration of membrane proteins into the cytoplasmic membrane.Received 10 January 2003; received after revision 2 April 2003; accepted 4 April 2003 相似文献
10.
The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis 总被引:3,自引:0,他引:3
The RAG1 and RAG2 proteins play a crucial role in V(D)J recombination by cooperating to make specific double-stranded DNA
breaks at a pair of recombination signal sequences (RSSs). However, the exact function they perform has heretofore remained
elusive. Using a combination of sensitive methods of sequence analysis, we show here that the active core region of the RAG2
protein, confined to the first three quarters of its sequence, is in fact composed of a six-fold repeat of a 50-residue motif
which is related to the kelch/mipp motif. This motif, which forms a four-stranded twisted antiparallel β sheet, is arranged in a circular formation like blades of a propeller or turbine. Given the known properties of the β-propeller fold in mediating protein-protein interactions, it is proposed that this six-laded propeller structure of the RAG2
active core would play a crucial role in the tight complex formed by the RAG1 and RAG2 proteins and RSSs. Moreover, the presence
of a plant homeodomain finger-like motif in the last quarter of the RAG2 sequence suggests a potential interaction of this
domain with chromatin components.
Received 6 June 1998; accepted 9 June 1998 相似文献
11.
Christian Piehl Jörg Piontek Jimmi Cording Hartwig Wolburg Ingolf E. Blasig 《Cellular and molecular life sciences : CMLS》2010,67(12):2131-2140
Tight junctions control paracellular permeability. Here, we analyzed the impact of residues in the second extracellular loop
(ECL2) of mouse claudin-5 on paracellular permeability. Stable expression of claudin-5wild type in MDCK-II cells—but not that of mutants R145A, Y148A, Y158A or E159Q—increased transepithelial electrical resistance and
decreased fluorescein permeation. Expression of claudin-5Y148A, Y158A or E159Q enhanced permeability of FITC-dextran10 kDa, which was unchanged in cells expressing claudin-5wild type or claudin-5R145A. In contrast, targeting to tight junctions, strand morphology and tight junction assembly were unchanged. It is concluded
that R145 is unessential for trans-interaction of claudin-5, but necessary for tightening against small solutes and ions. The highly conserved residues Y148,
Y158 and E159 in ECL2 of claudin-5 contribute to homo- and/or heterophilic trans-interaction between classic claudins and thereby tighten the paracellular space against ions, small and large molecules.
These results provide novel insights into the molecular function of tight junctions. 相似文献
12.
In vitro reconstitution of homologous recombination reactions 总被引:3,自引:0,他引:3
S. C. Kowalczykowski 《Cellular and molecular life sciences : CMLS》1994,50(3):204-215
The proteins essential to homologous recombination inE. coli have been purified and their individual activities have been identified, permitting biochemical reconstitution of steps that comprise the cellular recombination process. This review focuses on the biochemical events responsible for the initiation and homologous pairing steps of genetic recombination. The properties of an in vitro recombination reaction that requires the concerted action of recA, recBCD, and SSB proteins and that is stimulated by the recombination hotspot, Chi(), are described. The recBCD enzyme serves as the initiator of this reaction; its DNA helicase activity produces single-stranded DNA that is used by the recA protein to promote homologous pairing and DNA strand invasion of supercoiled (recipient) DNA. The SSB protein acts to trap the single-stranded DNA produced by recBCD enzyme and to facilitate pairing by the recA protein. The regulatory sequence acts incis by attenuating the nuclease, but not the helicase, activity of recBCD enzyme. This attenuation assures the preservation of ssDNA produced by the DNA helicase activity and is responsible for the simulation in vitro and, presumably, in vivo. The attenuation of nuclease activity by results in the loss or functional inactivation of the recD subunit. 相似文献
13.
Hydroxyproline-rich glycoproteins in plant reproductive tissues: structure, functions and regulation 总被引:10,自引:0,他引:10
H. Wu B. de Graaf C. Mariani A.Y. Cheung 《Cellular and molecular life sciences : CMLS》2001,58(10):1418-1429
The plant reproductive process of pollination involves a series of interactions between the male gametophyte (the pollen
grain or pollen tube) and extracellular matrix (ECM) molecules secreted by different cell types along the pollen tube growth
pathway in the female organ, the pistil. These interactions are believed to signal and regulate the pollen tube growth process
to effect successful delivery of the sperm cells to the ovules where fertilization takes place. Hydroxyproline-rich glycoproteins
secreted by plant cells are believed to play a broad range of functions, ranging from providing structural integrity to mediating
cell-cell interactions and communication. The pistil and pollen tube ECM is enriched in these highly glycosylated proteins.
Our discussions here will focus on a number of these proteins for which most information has been available, from Nicotiana tabacum, its self-incompatible relative N. alata, and Zea mays. In addition, the regulation of the synthesis and glyco-modification of one of these proteins, TTS (transmitting tissue-specific)
protein from N. tabacum will be discussed in the light of how differential glycosylation may be used to regulate molecular interactions within the
ECM. 相似文献
14.
Cell adhesion molecules (CAMs) have been implicated in the control of a wide variety of cellular processes, such as cell adhesion,
polarization, survival, movement, and proliferation. Nectins have emerged as immunoglobulin-like CAMs that participate in
calcium-independent cell-cell adhesion by homophilic and heterophilic trans-interactions with nectins and nectin-like molecules. Nectin-based cell-cell adhesion exerts its function independently or
in cooperation with other CAMs including cadherins and is essential for the formation of intercellular junctions, including
adherens junctions, tight junctions, and puncta adherentia junctions. Nectins cis-interact with integrin αvβ3 and platelet-derived growth factor receptor and facilitate their signals to regulate the formation and integrity of intercellular
junctions and cell survival. Nectins intracellularly associate with peripheral membrane proteins, including afadin and Par-3.
This review focuses on recent progress in understanding the interactions of nectins with other transmembrane and peripheral
membrane proteins to exert pleiotropic functions.
Received 27 June 2007; received after revision 14 August 2007; accepted 12 September 2007 相似文献
15.
Selective degradation of cellular proteins serves to eliminate abnormal proteins and to mediate the turnover of certain short-lived proteins, many of which have regulatory functions. In eukaryotes a major pathway for selective protein degradation is ATP-dependent and is mediated by the ubiquitin system. This pathway involves substrate recognition by components of a ubiquitin-protein ligase system, covalent attachment of ubiquitin moieties to proteolytic substrates, and subsequent degradation of these conjugates by a multicatalytic protease complex. Recent genetic evidence suggests that the remarkable selectivity of this process is largely controlled at the level of substrate recognition by the ubiquitin ligase system. InSaccharomyces cerevisiae, ubiquitin-conjugating enzymes UBC1, UBC4 and UBC5 have been identified as key components of this highly conserved degradation pathway. Genetic analysis indicates that ubiquitin-dependent proteolysis is essential for cell viability and that UBC4 and UBC5 enzymes are essential components of the eukaryotic stress response. 相似文献
16.
Hotspots of homologous recombination 总被引:9,自引:0,他引:9
G. R. Smith 《Cellular and molecular life sciences : CMLS》1994,50(3):234-241
Homologous recombination occurs at higher than average frequency at and near hotspots. Hotspots are special nucleotide sequences recognized by proteins that promote, directly or indirectly, a rate limiting step of recombination. This review focuses on two well-studied examples, the Chi sites of the bacteriumEscherichia coli and the M26 site of the fission yeastSchizosaccharomyces pombe. Chi, 5 G-C-T-G-G-T-G-G 3, is recognized by the RecBCD enzyme, which nicks the DNA near Chi and produces a 3-ended single-stranded DNA tail; this tail is a potent substrate for homologous pairing by RecA and single-stranded DNA binding proteins. M26, 5 A-T-G-A-C-G-T 3, is recognized by a heterodimeric protein and stimulates, by an as-yet-unknown mechanism, meiotic recombination at and near theade6 gene. Additional hotspots in bacteria, fungi, and mammals enhance recombination directly or indirectly via a variety of mechanisms. Although hotspots are widespread among organisms, the biological role of their localized enhancement of recombination remains a matter of speculation. 相似文献
17.
J. W. Bennett Phaik-Mooi Leong S. Kruger D. Keyes 《Cellular and molecular life sciences : CMLS》1986,42(7):848-851
Summary Serial transfer of mycelial macerates of a wild type, haploid, aflatoxigenic strain ofAspergillus parasiticus in a defined liquid medium resulted in the production of three new morphological classes: a sclerotial form with high aflatoxin production, and two variant forms (fan andfluff) with lowered sporulation, no sclerotia, and attenuated levels of aflatoxin. A genetically marked diploid containing mutant markers for aflatoxin pathway intermediates yielded the same three morphological classes upon serial transfer of macerated mycelia. When these diploid variants were treated with a haploidization agent, and the phenotypes of the resultant segregants scored, a low frequency of colonies producing aflatoxin pathway intermediates was recovered. These genetic data indicate that the structural genes for the aflatoxin pathway are present but somehow attenuated in thefan andfluff strains.This work was supported by a Cooperative Agreement from the U.S. Department of Agriculture, (58-7B30-3-556). 相似文献
18.
SecB is only one of a plethora of cytosolic chaperones in E. coli whose common property is that they bind nonnative proteins. It plays a crucial role during protein export via the general
secretory pathway by modulating the partitioning of precursors between folding or aggregation and delivery to the membrane-bound
translocation apparatus. In this latter role SecB demonstrates specific binding to a unique partner, SecA. SecB has the potential
to participate in functions outside of export acting as a general nonspecific chaperone to provide buffering capacity of the
nonnative state of proteins in the cytosolic pool. We discuss the interactions of SecB with its many binding partners in light
of its recently determined structure, emphasizing both kinetic and thermodynamic parameters.
RID="*"
ID="*"Corresponding author. 相似文献
19.
A. Fridkin A. Penkner V. Jantsch Y. Gruenbaum 《Cellular and molecular life sciences : CMLS》2009,66(9):1518-1533
20.
Elisabetta Meacci Francesca Bini Chiara Sassoli Maria Martinesi Roberta Squecco Flaminia Chellini Sandra Zecchi-Orlandini Fabio Francini Lucia Formigli 《Cellular and molecular life sciences : CMLS》2010,67(24):4269-4285
We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions
and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel
activity with Cx43 expression/function, investigating the involvement of the Ca2+-sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of
TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P. TRPC1-dependent functions
were also required for the transient increase of m-calpain activity/expression and the subsequent decrease of PKCα levels. Remarkably, Cx43 expression in S1P-treated myoblasts
was reduced by m-calpain-siRNA and enhanced by pharmacological inhibition of classical PKCs, stressing the relevance for calpain/PKCα axis
in Cx43 protein remodeling. The contribution of this pathway in myogenesis was also investigated. In conclusion, these findings
provide novel mechanisms by which S1P regulates myoblast differentiation and offer interesting therapeutic options to improve
skeletal muscle regeneration. 相似文献