ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2318378

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Evidence implicating molecular steps in memory storage is discussed, particularly with reference to molecular specificity and uniqueness and the possible relevance of these steps to other types of long‐lasting transformations such as those of development, regeneration, and tumorigenesis. The role of protein kinase C‐mediated phosphorylation of identified protein subtrates, such as a 20,000‐dalton GTP‐binding protein, is described for associative memory of the snailHermissenda, associative conditioning of the rabbit, and long‐term potentiation. Cyclic AMP‐mediated phosphorylation during sensitization of the snailAplysiais also examined.— Alkon, D. L.; Nelson, T. J. Specificity of molecular changes in neurons involved in memory storage.FASEB J.4: 1567‐1576; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2108074

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Basement membranes are specialized extracellular matrices with support, sieving, and cell regulatory functions. The molecular architectures of these matrices are created through specific binding interactions between unique glycoprotein and proteoglycan protomers. Type IV collagen chains, using NH2‐terminal, COOH‐terminal, and lateral association, form a covalently stabilized polygonal framework. Laminin, a four‐armed glycoprotein, self‐assembles through terminal‐domain interactions to form a second polymer network, Entactin/nidogen, a dumbbell‐shaped sulfated glycoprotein, binds laminin near its center and interacts with type IV collagen, bridging the two. A large heparan sulfate proteoglycan, important for charge‐dependent molecular sieving, is firmly anchored in the basement membrane and can bind itself through a core‐protein interaction to form dimers and oligomers and bind laminin and type IV collagen through its glycosaminoglycan chains. Heterogeneity of structure and function occur in different tissues, in development, and in response to different physiological needs. The molecular architecture of these matrices may be regulated during or after primary assembly through variations in compositions, isoform substitutions, and the modifying influence of exogenous macromolecules such as heparin and heparan sulfate.— Yurchenco, R D.; Schittny, J. C. Molecular architecture of basement membranes.FASEB J.4: 1577‐1590; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2180767

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Protozoa contain thymidylate synthase (TS) and dihydrofolate reductase (DHFR) on the same polypeptide. In the bifunctional protein, the DHFR domain is on the amino terminus, TS is on the carboxyl terminus, and the two domains are separated by a junction peptide of varying size depending on the source. The native protein is composed of a dimer of two such subunits and is 110‐140 kDa. Most studies of the bifunctional TS‐DHFR have been performed with the protein from anti‐folate resistant strains ofLeishmania major, which show amplification of the TS‐DHFR gene and overproduction of the bifunctional protein. TheLeishmaniaTS‐DHFR has also been highly expressed in heterologous systems. There appears to be extensive communication among domains and channeling of the H2folate product of TS to DHFR. Anti‐folates commonly used to treat microbial infections are poor inhibitors ofL. majorDHFR. However, selective inhibition ofL. majorvs. human DHFR does not appear difficult to achieve, and selective inhibitors are known. The TS‐DHFR fromPlasmodium falciparumhas also been cloned and has recently been expressed inEscherichia coli, albeit in small amounts. Interestingly, pyrimethamine‐resistant strains ofP. falciparumall have a common point mutation in the DHFR coding sequence (Thr/Ser 108 to Asn), which causes decreased binding of the folate analog. It is suggested that if an appropriate inhibitor of the pyrimethamine‐resistantP. falciparumDHFRs can be found, it may serve in combination with pyrimethamine as an antimalarial regimen with low propensity for the development of resistance. In the future, we project that we will have a detailed knowledge of the structure and function of TS‐DHFRs, and have the essential tools necessary for a molecular‐based approach to drug design.— Ivanetich, K. M.; Santi, D. V. Bifunctional thymidylate synthase‐dihydrofolate reductase in protozoa.FASEB J.4: 1591‐1597; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2180768

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The sodium pump Na,K‐ATPase, located in the plasma membrane of all animal cells, is a member of a family of ion‐translocating ATPases that share highly homologous catalytic subunits. In this family, only Na,K‐ATPase has been established to be a heterodimer of catalytic (α) and glycoprotein (β) subunits. The β subunit has not been associated with the pump's transport or enzymatic activity, and its role in Na,K‐ATPase function has been, until recently, a puzzle. In this review we describe what is known about the structure of β and summarize evidence that expression of both a and β subunits is required for Na,K‐ATPase activity, that inhibition of glycosylation causes a decrease in accumulation of both α and β subunits, and we provide evidence that pretranslational up‐regulation of β alone can lead to increased abundance of sodium pumps. These findings are all consistent with the hypothesis that the β subunit regulates, through assembly of αβ heterodimers, the number of sodium pumps transported to the plasma membrane.— McDonough, A. A.; Geering, K.; Farley, R. A. The sodium pump needs its β subunit.FASEB J.4: 1598‐1605; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2156741

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The tachykinins comprise a family of closely related peptides that participate in the regulation of diverse biological processes. The tachykinin peptides substance P, neurokinin A, neurokinin A(3‐10), neuropeptide K, and neuropeptide γ are produced from a single preprotachykinin gene as a result of differential RNA splicing and differential posttranslational processing. Another tachykinin, neurokinin B, is produced from a separate preprotachykinin gene. These preprotachykinin mRNAs and peptide products are differentially distributed throughout the nervous system. Three distinct G protein‐coupled tachykinin receptors exist for these tachykinin peptides. The three receptors interact differentially with the tachykinin peptides and are uniquely distributed throughout the nervous system. The NK‐1 receptor preferentially interacts with substance P, the NK‐2 receptor prefers neurokinin A, neuropeptide K, and neuropeptide γ, and the NK‐3 receptor interacts best with neurokinin B. Examples of the roles of tachykinin peptidergic neuronal systems are taken from the spinal cord sensory system and the nigrostriatal extrapyramidal motor system. Analysis of the functional significance of multiple tachykinin peptide systems, receptor‐second messenger coupling mechanisms, and developmental and regulatory mechanisms underlying peptide mRNA and receptor expression represent areas of current and future investigation.—Helke, C. J.; Krause, J. E.; Mantyh, P. W.; Couture, R.; Bannon, M. J. Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms.FASEB J.4: 1606‐1615; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.1969374

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The collagens represent a family of structurally related but genetically distinct proteins whose function is essential to maintaining the integrity of vertebrate organs. In addition to their supportive roles, collagens influence a variety of developmental programs and physiological processes. Transcription of collagen genes is controlled by a series of complex interactions betweencis‐acting regulatory elements andtrans‐acting nuclear factors that have positive or negative effects on gene expression. Collagen synthesis relies on the timely utilization of diversified regulatory programs that employ tissue and cell‐type specific promoters and enhancers. Some of these programs lead to the production of structurally variant chains in different tissues, while others shut down synthesis of a specific collagen type during cell differentiation. Still others control collagen expression in distinct cell lineages. The number, complexity, and variety of the mechanisms leading to the diversified expression of the collagen genes illustrate the unique contribution of this family of proteins to multicellular organogenesis.— Ramirez, F.; DiLiberto, M. Complex and diversified regulatory programs control the expression of vertebrate collagen genes.FASEB J.4: 1616‐1623; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2180769

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Using the N18‐RE‐105 neuroblastoma X retina cell line, we previously described Ca2+‐dependent quisqualate‐type glutamate toxicity caused by the inhibition of high‐affinity cystine uptake, leading to glutathione depletion and accumulation of cellular oxidants. We now demonstrate that primary cultures of rat cortical neurons (E17; 24‐72 h in culture), but not glia, also degenerate when exposed to culture medium with reduced cystine or containing competitive inhibitors of cystine uptake, including glutamate. At this developmental stage, neurotoxicity did not occur as a consequence of continuous exposure to glutamate receptor subtype agonists,N‐methyl‐d‐aspartate, kainate, or 2(RS)‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropioniate. However, those that inhibited neuronal cystine uptake — quisqualate, glutamate, homocysteate, β‐N‐oxalyl‐l‐α,β‐diaminopropionic acid, and ibotenate—were neurotoxic. Toxicity related to quisqualate did not correlate with the development of quisqualate‐stimulated phosphatidylinositol turnover. The toxic potencies of glutamate, quisqualate, and homocysteate were inversely proportional to the concentration of cystine in the medium, suggesting that they competitively inhibit cystine uptake. Autoradiographic analysis of the cellular localization ofl‐[35S]cystine uptake indicated that embryonic neurons have a high‐affinity transport system that is sensitive to quisqualate, whereas nonneuronal cells in the same cultures have a low‐affinity system that is insensitive to quisqualate but potently blocked byd‐aspartate and glutamate. Exposure to glutamate or homocysteate resulted in a time‐dependent depletion of the cellular antioxidant glutathione. The centrally acting antioxidant idebenone and α‐tocopherol completely blocked the neurotoxicity resulting from glutamate exposure. We propose that competitive inhibition of cystine transport and reduction of extracellular cystine levels result in neuronal cell death due to accumulation of cellular oxidants.— Murphy, T. H.; Schnaar, R. L.; Coyle, J. T. Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake.FASEB J.4: 1624‐1633; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2180770

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The mechanism by which cells increase their rate of glucose uptake in response to stress is unclear. Using an immunofluorescence technique to localize the glucose transporter protein in BHK cells, we found that hyperthermia, treatment with arsenite, infection with vesicular stomatitis virus or Semliki Forest virus, and treatment with insulin cause the transporter to move from an intracellular site in the perinuclear region to the plasma membrane; the degree of translocation correlates approximately with the increase in glucose uptake. We conclude that stress induces an insulin‐like distribution of certain membrane proteins.— Widnell, C. C.; Baldwin, S. A.; Davies, A.; Martin, S.; Pasternak, C. A. Cellular stress induces a redistribution of the glucose transporter.FASEB J.4: 1634‐1637; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2156742

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

The fluorescent probe, fura 2, is widely used to measure agonist‐induced changes in intracellular calcium concentration ([Ca2+]i) in cultured cells. However, in many instances, the results obtained in the same cell type have differed from one study to the next. The possibility that such differences might be due to experimental conditions was examined by using fura 2 in four different cell types responding to appropriate agonists when the cells were incubated in either CO2/HCO3−‐ or HEPES‐buffered media. Examined were:1) the response of rat glomerular mesangial cells to arginine vasopressin,2) the response of vascular smooth muscle cells to angiotensin II,3) the response of adrenal glomerulosa cells to angiotensin II, and4) the response of hypothalamic cells to insulin‐like growth factor‐1. In each cell type there was a significant difference in the pattern of agonist‐induced change in [Ca2+]iwhen HEPES vs. CO2/HCO3−was used as the buffer system: in HEPES buffer, agonist addition led to a transient rise in [Ca2+]ifollowed by a fall to a sustained plateau 27 to 34 nM higher than the original basal value, whereas in CO2/HCO3−buffer, agonist addition led to an identical transient increase in [Ca2+]ifollowed by a fall to a value within 10 nM or less of the preagonist level. The plateau value of [Ca2+]iin the different buffers was examined in relationship to known differences in intracellular pH (pHi). It was found that measurements of [Ca2+]iwith fura 2 were influenced by shifts in pHithat occur when cells are incubated in either HEPES‐buffered or CO2/HCO3−media of differing pHovalues. However, at any given value of pHi, the apparent [Ca2+]imeasured in cells incubated in HEPES‐buffered media was slightly higher than in cells incubated in CO2/HCO3‐buffered media.— Ganz, M. B.; Rasmussen, J.; Bollag, W. B.; Rasmussen, H. Effect of buffer systems and pHi on the measurement of [Ca2+]iwith fura 2.FASEB J.4: 1638‐1644; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.6.2318379

出版商:Wiley    

年代:1990

数据来源: WILEY