Scaffolding Protein (scaffolding + protein)

Distribution by Scientific Domains


Selected Abstracts


Scaffolding proteins organize multimolecular protein complexes for sensory signal transduction

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2001
Armin Huber
Abstract Scaffolding proteins composed of protein,protein interaction domains have emerged as organizers of multiprotein complexes in diverse cellular compartments, including neuronal synapses, cell,cell junctions of epithelial cells, and the stimulus perceiving structures of sensory neurons. This review focuses on the INAD-assembled signalling complex of Drosophila photoreceptors, which organizes key components of the phototransduction cascade into a multiprotein signal transduction unit. The structure, the physiological consequences, and the assembly and targeting of the members of the INAD signalling complex will be described. In addition, the existence of signalling complexes in vertebrate photoreceptors, olfactory neurons and mechanosensitive hair cells will be discussed. [source]


Adherens junctions: new insight into assembly, modulation and function

BIOESSAYS, Issue 8 2002
Ulrich Tepass
Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1,3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.5 BioEssays 24:690,695, 2002. © 2002 Wiley Periodicals, Inc. [source]


Neural plasticity and addiction: integrin-linked kinase and cocaine behavioral sensitization

JOURNAL OF NEUROCHEMISTRY, Issue 3 2008
Qiang Chen
Abstract Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of biochemical molecules in different brain regions. However, which change is actually related to drug-produced sensitization lacks of accurate clarification. In this study, we investigated the role of integrin-linked kinase (ILK) in both the induction and expression of cocaine sensitization. Conditional inhibition of ILK expression was established in the nucleus accumbens (NAc) core by microinjecting recombinant adeno-associated virus-carrying, tetracycline-on-regulated small interfering RNA which reversed the chronic cocaine-induced psychomotor sensitization, as well as the changes in protein kinase B Ser473 phosphorylation, dendritic density, and dendritic spine numbers locally. Importantly, the reversed psychomotor sensitization did not recover after cessation of the silencing for 8 days. We also demonstrated that inhibition of ILK expression pre- and during-chronic cocaine treatments blocked the induction of cocaine psychomotor sensitization and abolished the stimulant effect of cocaine on ILK expression. In contrast, inhibition of ILK expression in the NAc core has no significant effect on cocaine-induced stereotypical behaviors. This concludes that ILK is involved in cocaine sensitization with the earlier induction and later expression functioning as a kinase to regulate protein kinase B Ser473 phosphorylation and a scaffolding protein to regulate the reorganization of the NAc spine morphology. [source]


Determinants of bacteriophage P22 polyhead formation: the role of coat protein flexibility in conformational switching

MOLECULAR MICROBIOLOGY, Issue 6 2010
Margaret M. Suhanovsky
Summary We have investigated determinants of polyhead formation in bacteriophage P22 in order to understand the molecular mechanism by which coat protein assembly goes astray. Polyhead assembly is caused by amino acid substitutions in coat protein at position 170, which is located in the ,-hinge. In vivo scaffolding protein does not correct polyhead assembly by F170A or F170K coat proteins, but does for F170L. All F170 variants bind scaffolding protein more weakly than wild-type as observed by affinity chromatography with scaffolding protein-agarose and scaffolding protein shell re-entry experiments. Electron cryo-microscopy and three-dimensional image reconstructions of F170A and F170K empty procapsid shells showed that there is a decreased flexibility of the coat subunits relative to wild-type. This was confirmed by limited proteolysis and protein sequencing, which showed increased protection of the A-domain. Our data support the conclusion that the decrease in flexibility of the A-domain leads to crowding of the subunits at the centre of the pentons, thereby favouring the hexon configuration during assembly. Thus, correct coat protein interactions with scaffolding protein and maintenance of sufficient coat protein flexibility are crucial for proper P22 assembly. The coat protein ,-hinge region is the major determinant for both features. [source]


Cellulosomes: microbial nanomachines that display plasticity in quaternary structure

MOLECULAR MICROBIOLOGY, Issue 6 2007
Harry J. Gilbert
Summary The assembly of proteins that display complementary activities into supramolecular intra- and extracellular complexes is central to cellular function. One such nanomachine of considerable biological and industrial significance is the plant cell wall degrading apparatus of anaerobic bacteria termed the cellulosome. The Clostridium thermocellum cellulosome assembles through the interaction of a type I dockerin module in the catalytic entities with one of several type I cohesin modules in the non-catalytic scaffolding protein. Recent structural studies have provided the molecular details of how dockerin,cohesin interactions mediate both cellulosome assembly and the retention of the protein complex on the bacterial cell surface. The type I dockerin, which displays near-perfect sequence and structural symmetry, interacts with its cohesin partner through a dual binding mode in which either the N- or C-terminal helix dominate heterodimer formation. The biological significance of this dual binding mode is discussed with respect to the plasticity of the orientation of the catalytic subunits within this supramolecular assembly. The flexibility in the quaternary structure of the cellulosome may reflect the challenges presented by the degradation of a heterogenous recalcitrant insoluble substrate by an intricate macromolecular complex, in which the essential synergy between the catalytic subunits is a key feature of cellulosome function. [source]


Crystallization and initial X-ray diffraction studies of scaffolding protein (gp7) of bacteriophage ,29

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2005
Dwight L. Anderson
The Bacillus subtilis bacteriophage ,29 scaffolding protein (gp7) has been crystallized by the hanging-drop vapour-diffusion method at 293,K. Two new distinct crystal forms that both differed from a previously crystallized and solved scaffolding protein were grown under the same conditions. Form I belongs to the primitive tetragonal space group P41212, with unit-cell parameters a = b = 77.13, c = 37.12,Å. Form II crystals exhibit an orthorhombic crystal form, with space group C222 and unit-cell parameters a = 107.50, b = 107. 80, c = 37.34,Å. Complete data sets have been collected to 1.78 and 1.80,Å for forms I and II, respectively, at 100,K using Cu,K, X-rays from a rotating-anode generator. Calculation of a VM value of 2.46,Å3,Da,1 for form I suggests the presence of one molecule in the asymmetric unit, corresponding to a solvent content of 50.90%, whereas form II has a VM of 4.80,Å3,Da,1 with a solvent content of 48.76% and two molecules in the asymmetric unit. The structures of both crystal forms are being determined by the molecular-replacement method using the coordinates of the published crystal structure of gp7. [source]


Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007
Elaine C. Budreck
Abstract Synaptic adhesion molecules are thought to play a critical role in the formation, function and plasticity of neuronal networks. Neuroligins (NL1,4) are a family of presumptive postsynaptic cell adhesion molecules. NL1 and NL2 isoforms are concentrated at glutamatergic and GABAergic synapses, respectively, but the cellular expression and synaptic localization of the endogenous NL3 and NL4 isoforms are unknown. We generated a panel of NL isoform-specific antibodies and examined the expression, developmental regulation and synaptic specificity of NL3. We found that NL3 was enriched in brain, where NL3 protein levels increased during postnatal development, coinciding with the peak of synaptogenesis. Subcellular fractionation revealed a concentration of NL3 in synaptic plasma membranes and postsynaptic densities. In cultured hippocampal neurons, endogenous NL3 was highly expressed and was localized at both glutamatergic and GABAergic synapses. Clustering of NL3 in hippocampal neurons by neurexin-expressing cells resulted in coaggregation of NL3 with glutamatergic and GABAergic scaffolding proteins. Finally, individual synapses contained colocalized NL2 and NL3 proteins, and coimmunoprecipitation studies revealed the presence of NL1,NL3 and NL2,NL3 complexes in brain extracts. These findings suggest that rodent NL3 is a synaptic adhesion molecule that is a shared component of glutamatergic and GABAergic synapses. [source]


Protein aggregation in postsynaptic density after transient brain ischemia

JOURNAL OF NEUROCHEMISTRY, Issue 2003
M. Ber, sewicz
Brief cerebral ischemia causes changes in synaptic transmission and in consequence in neuronal function manifested in delayed cell death of CA1 hippocampal region. Postsynaptic density (PSD) is composed by a network of interacting proteins, including scaffolding proteins, neurotransmitter receptors, cytoskeletal proteins and protein kinases. PSD dynamically modulates signal transduction what influence the cell fate. We investigated the composition of the PSD network and effect of ischemia on its complexity. Two experimental procedures were applied. The interaction between PSD-95 and Src, Fyn, Raf-1, paxilin or NMDA receptor subunits were explored using coimmunoprecipitation method. In addition, the effect of ischemia-reperfusion on the density of PSD were evaluated by measurement of is solubility. We find out the decrease in solubility of the PSD-95, NR2A, NR2B and Raf-1. Of interest, the latter was restricted to surviving regions of hippocampus. Acknowledgement:, Financed by PBZ-KBN-002/CD/P05/2000. [source]


The Risk of Cardiac Events and Genotype-Based Management of LQTS Patients

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009
Ph.D., oskot M.D., yna Markiewicz-
This review discusses the risk of cardiac events and genotype-based management of LQTS. We describe here the genetic background of long QT syndrome and the eleven different genes for ion-channels and a structural anchoring protein associated with that disorder. Clinical Background section discusses the risk of cardiac events associated with different LQTS types. Management and Prevention section describes in turn gene-specific therapy, which was based on the identification of the gene defect and the dysfunction of the associated transmembrane ion channel. In patients affected by LQTS, genetic analysis is useful for risk stratification and for making therapeutic decisions. A recent study reported a quite novel pathogenic mechanism for LQTS and suggested that treatments aimed at scaffolding proteins rather than specific ion channels may be an alternative to antiarrhythmic strategy in the future. [source]


,-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction

BRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2008
K DeFea
G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors (7-TMRs), are the largest protein receptor superfamily in the body. These receptors and their ligands direct a diverse array of physiological responses, and hence have broad relevance to numerous diseases. As a result, they have generated considerable interest in the pharmaceutical industry as drug targets. Recently, GPCRs have been demonstrated to elicit signals through interaction with the scaffolding proteins, ,-arrestins-1 and 2, independent of heterotrimeric G-protein coupling. This review discusses several known G-protein-independent, ,-arrestin-dependent pathways and their potential physiological and pharmacological significance. The emergence of G-protein-independent signalling changes the way in which GPCR signalling is evaluated, from a cell biological to a pharmaceutical perspective and raises the possibility for the development of pathway specific therapeutics. British Journal of Pharmacology (2008) 153, S298,S309; doi:10.1038/sj.bjp.0707508; published online 26 November 2007 [source]