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PubMed1990

The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding.

The interaction of actin with a synthetic peptide which corresponds to one of the repeated tubulin-binding sites present in tau and MAP-2 (microtubule-associated protein 2) proteins has been analysed. The analysis, which uses affinity chromatography of G-actin on a column containing the synthetic peptide, and the co-sedimentation and co-localization of F-actin and the peptide (as determined by immunoelectron microscopy), indicates that the part of the amino acid sequence of tau involved in the binding of tubulin is also involved in actin binding.

Actins↗
PubMedDate not supplied

Limb girdle muscular dystrophy type 2A (CAPN3): mapping using allelic association.

Recently a graphical study of linkage disequilibrium around the CAPN3 locus failed to refine the 1.3-Mb interval suggested by haplotype sharing. On the contrary, the Malecot model as implemented in the ALLASS program maps CAPN3 within 3 kb of its true location (23 kb from the locus midpoint), overcoming identified problems with small samples, interrelated sibships, and short duration.

Alleles↗
PubMed1976

Partial deletions and trisomies of chromosome 13; mapping of bands associated with particular malformations.

New techniques of human karyotyping have allowed us to define accurately the banding pattern of six new cases with partial duplication of deficiency of chromosome 13. It now seems possible to draw a rough map of chromosome 13, correlating observed malformations and phenotypic features with specific chromosome regions. Partial monosomy shows clinical features which are the antithesis of the corresponding trisomic phenotype (Lejeune 1966).

Abnormalities, Multiple↗
PubMed1995

Human microtubule-associated protein-2c localizes to dendrites and axons in fetal spinal motor neurons.

Microtubule-associated protein-2 (MAP-2) functions to maintain neuronal morphology by promoting the assembly of microtubules. MAP-2c is an alternately spliced form of MAP-2, containing the first 151 amino acids of high-molecular-weight (HMW) MAP-2 joined to the last 321 amino acids, eliminating 1,352 amino acids specific to HMW MAP-2. A polyclonal antibody generated to the splice site of human MAP-2c was used to determine its cellular localization. The MAP-2c antiserum was depleted of any HMW MAP-2 reactivity by absorption with HMW MAP-2 fusion protein. Western blot analysis of human fetal spinal cord homogenates demonstrated that the antibody is specific for human MAP-2c. MAP-2c immunoreactivity was found in the perinuclear cytoplasm and processes of anterior motor neurons and large processes of the posterior column in sections from 22-24-week human fetal spinal cord. Double-label confocal microscopy was performed using the MAP-2c polyclonal antibody and either a HMW MAP-2 or a neurofilament protein (highly phosphorylated 160- and 200-kDa protein) monoclonal antibody to identify these processes as dendrites or axons, respectively. HMW MAP-2 and MAP-2c colocalized in cell bodies and dendrites of anterior motor neurons, demonstrating for the first time the presence of native MAP-2c within dendrites. In addition, immunoelectron microscopy showed MAP-2c associated with microtubules in dendrites of motor neurons. MAP-2c and the neurofilament proteins were found in axons of the dorsal and ventral roots. The presence of MAP-2c within axons and dendrites suggests that MAP-2c contributes to neuronal plasticity during human fetal development.

Axons↗
PubMed1990

Peptides corresponding to the second repeated sequence in MAP-2 inhibit binding of microtubule-associated proteins to microtubules.

Bovine brain high molecular weight microtubule-associated proteins (MAPs) can be displaced from assembled tubules by peptides corresponding to the second of three nonidentical repeated sequences in mouse MAP-2. The octadecapeptide m2 (VTSKCGSLKNIRHRPGGG) can release MAP-1b from MAP-containing microtubules, and the extended second-sequence peptide m2' (VTSKCGSLKNIRHRPGGGRVK) displaces MAP-1a and MAP-1b as well as MAP-2a and MAP-2b. Peptides m2 and m2' stimulate tubulin polymerization in the absence of MAPs or microtubule-stabilizing agents, and m2' acts as a competitive inhibitor of radiolabeled MAP-2 binding. The dissociation constant for MAP-2 binding to taxol-stabilized tubules was 3.4 microM in the absence of m2' and 14 microM in the presence of 1.5 mM of the m2' peptide. We estimate that the inhibition constant for peptide m2' is about 0.5 mM, about 100 times lower than for the Km of MAP-2. These observations suggest that the second repeated sequence in MAP-2 may represent an important recognition site for MAP binding to microtubules and that other structural features within MAP-2 may reinforce the strength of MAP-microtubule interactions.

Amino Acid Sequence↗
PubMed2002

Carnitine prevents NMDA receptor-mediated activation of MAP-kinase and phosphorylation of microtubule-associated protein 2 in cerebellar neurons in culture.

Activation of N-methyl-D-aspartate (NMDA) receptors leads to increased phosphorylation of the microtubule-associated protein MAP-2 by a mechanism that involves activation of nitric oxide synthase and nitric oxide-induced activation of mitogen-activated protein kinase (MAP-kinase). We have assessed the effects of carnitine on this signal transduction pathway in primary cultures of rat cerebellar neurons. We show that carnitine inhibits NMDA-induced phosphorylation of MAP-2 and that this is due to decreased activation of MAP-kinase. This effect is not due to inhibition by carnitine of NMDA-induced activation of nitric oxide synthase or to quenching of the nitric oxide formed, which are not affected by carnitine. Carnitine also inhibits the increase in phosphorylation of MAP-2 induced by the nitric oxide-generating agent S-nitroso-N-acetylpenicillamine, but not nitric oxide-induced activation of soluble guanylate cyclase. These results indicate that carnitine interferes with NMDA-induced, nitric oxide mediated activation of MAP-kinase at a step subsequent to nitric oxide formation.

Animals↗
PubMed1997

MAP 0, a 400-kDa microtubule-associated protein unique to teleost fish.

Microtubules from neural tissues of the Atlantic cod, Gadus morhua, and of several species of Antarctic teleosts are composed of tubulin and several microtubule-associated proteins (MAPs), one of which has an apparent molecular weight of approximately 400-430 kDa. Because its apparent molecular weight exceeds those of the MAP 1 proteins, we designate this high molecular weight teleost protein MAP 0. Cod MAP 0 failed to cross-react with antibodies specific for MAPs 1A, 1B and 2 of mammalian brain, for MAP H1 of squid optic lobe, and for chicken erythrocyte syncolin, which suggests that it has a novel structure. Similarly, MAP 0 from the Antarctic fish was not recognized by an antibody specific for bovine MAP 2. Together, these observations suggest that MAP 0 is a novel MAP that may be unique to fish. To determine the tissue specificity and phylogenetic distribution of this protein, we generated a rabbit polyclonal antibody against cod MAP 0. Using this antibody, we found that MAP 0 was present in microtubule proteins isolated from cod brain tissues and spinal cord but was absent in microtubules from heart, liver, and spleen. At the subcellular level, MAP 0 was distributed in cod brain cells in a punctate pattern coincident with microtubules but was absent in skin cells. MAP 0 was also detected in cells of the peripheral nervous system. A survey of microtubule proteins from chordates and invertebrates showed that anti-MAP 0-reactive homologs were present in five teleost species but not in more primitive fish and invertebrates or in higher vertebrates. MAP 0 bound to cod microtubules by ionic interaction at a site recognized competitively by bovine MAP 2. Although its function is unknown, MAP 0 does not share the microtubule-binding properties of the motor proteins kinesin and dynein. We propose that MAP 0 is a unique, teleost-specific MAP.

Amphibians↗
PubMed2002

Genetic mapping of QTLs associated with greenbug resistance and tolerance in Sorghum bicolor.

Ninety three recombinant inbreds of Sorghum bicolor (L. Moench) were derived from a cross between two sorghum lines GBIK and Redlan. This population was used to identify quantitative trait loci (QTLs) for resistance and tolerance to greenbug ( Schizaphids graminum Rondani) Biotypes I and K. One hundred and thirteen loci (38 SSRs and 75 RAPDs) were mapped in 12 linkage groups covering 1,530 cM. In general, nine QTLs were detected affecting both resistance and tolerance to greenbug (GB) Biotypes I and K. The phenotypic variance explained by each QTL ranged from 5.6% to 38.4%. Four SSRs and one RAPD marker were associated with the expression of all resistance and tolerance traits. These markers appear to be linked to biotype non-specific resistance and tolerance genes. Four additional markers were associated with biotype-specific resistance or tolerance traits. The detection of more than one locus for each biotype supports the hypothesis that several regions, which represent different genes, control the expression of resistance and tolerance to greenbug in sorghum. The results can be used for marker-assisted selection and the breeding of greenbug-tolerant sorghum cultivars.

Journal Article↗
PubMed2002

Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1.

Ichthyosis vulgaris (IV) is a mild to severe scaling disorder of uncertain etiology estimated to affect as many as 1 : 250 in the population. Family studies have shown that in many cases IV follows an autosomal dominant inheritance pattern, but gene mapping studies have not been reported. To investigate the genetic basis for inherited IV, we have performed gene linkage studies in two multigenerational families where affected individuals have clinical features of IV but distinct histological features. The epidermis in this disorder characteristically displays non-specific orthohyperkeratosis. Notably, a subset of IV patients with a reduced or absent granular epidermal layer (AGL) have been reported, and decreased filaggrin levels have been described in others. The prominent role of profilaggrin in human keratohyalin suggests that defects in the gene for profilaggrin (FLG), its processing of profillagrin to filaggrin, or a gene involved in profilaggrin regulation may underlie or modify the pathology in IV. Family 1 had seven individuals with IV, severe heat intolerance and epidermis with 1-3 granular layers (consistent with normal epidermal histology). Ichthyosis vulgaris in this family did not segregate with FLG or other genes in the epidermal differentiation complex. In contrast, five of the six IV patients in Family 2, all siblings, had epidermis with no granular layer. Significant evidence was obtained for linkage of IV with the associated AGL phenotype to the epidermal differentiation complex (which includes FLG) assuming either a recessive (max Lod 3.4) or dominant (max Lod 3.6) inheritance model. Sequence analysis of FLG did not reveal a mutation in the amino or carboxyl terminal portions of the coding sequence adjacent to filaggrin repeats. The AGL may represent an endophenotype for IV, and the presence of a modifier of IV pathology at this locus is discussed.

Adult↗
PubMed1994

Purification and characterization of the high molecule weight microtubule associated proteins from neonatal rat brain.

The changes in the levels of microtubule-associated proteins (MAPs) during advanced embryonic stages, neonatal and adult organisms reflect the importance of these cytoskeletal proteins in relation to the morphogenesis of the central nervous system. MAP-1B is found in prenatal brains and it appears to have the highest levels in neonatal rat brains, being a developmentally-regulated protein. In this research, a fast procedure to isolate MAP-1B, as well as MAP-2 and MAP-3 from neonatal rat brains was designed, based on the differential capacity of poly L-aspartic acid to release MAPs during temperature-dependent cycles of microtubule assembly in the absence of taxol. The high molecular weight MAP-1B was recovered in the warm supernatants after microtubular protein polymerization in the presence of low concentrations of polyaspartic acid. Instead, MAP-2 and a 180 kDa protein with characteristics of MAP-3 remained associated to the polymer after the assembly. Further purification of MAP-1B was attained after phosphocellulose chromatography. Isolation of MAP-2 isoforms together with MAP-3 was achieved on the basis of their selective interactions with calmodulin-agarose affinity columns. In addition, MAP-2 and MAP-3 were also purified on the basis of their capacities to interact with the tubulin peptide beta-II (422-434) derivatized on an Affigel matrix. However, MAP-1B did not interact with the beta-II tubulin fragment, but it showed interaction with the Affigel-conjugated beta-I (431-444) tubulin peptide. The different MAPs components were characterized by western blots using specific monoclonal antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Constitutive up-regulated activity of MAP kinase is associated with down-regulated early p21Ras pathway in lymphocytes of SLE patients.

Aberrant expression of the p21Ras proto-oncogene has been reported in lymphoid cells of SLE patients. We previously showed that the expression of the p21Ras stimulatory element, hSOS1, is reduced in PBMC from SLE patients with non-active disease. However, the significance of this finding regarding the regulation and function of the p21Ras pathway and its correlation to disease activity remained unclear. The expression, regulation and function of the p21Ras pathway were determined in 23 ambulatory SLE patients with active and non-active disease and eleven controls. Levels of p21Ras stimulatory element hSOS1 but not p21Ras and its inhibitory element p120GAP were significantly decreased in SLE patients. Early p21Ras signalling was down-regulated in SLE patients with active disease as indicated by the decreased membrane/cytoplasmic (M/C) ratios of the p21Ras regulatory elements hSOS1 and p120GAP and by the non-responsiveness of these ratios to cellular stimulation. Anchorage of p21Ras to the cellular membrane was also significantly decreased in these patients. In contrast, the late p21Ras signalling was up-regulated in SLE patients as indicated by the significantly higher constitutive activity of the p21Ras down stream key regulator enzyme MAP Kinase. Taken together, our data demonstrate for the first time a disease associated functional defect in p21Ras signalling in lymphocytes of SLE patients.

Adult↗
PubMed2005

The effect of missing data on linkage disequilibrium mapping and haplotype association analysis in the GAW14 simulated datasets.

We used our newly developed linkage disequilibrium (LD) plotting software, JLIN, to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated population to assess the effect of missing data on LD calculations. Our haplotype analysis program, SIMHAP, was used to assess the effect of missing data on haplotype-phenotype association. Genotype data was removed at random, at levels of 1%, 5%, and 10%, and the LD calculations and haplotype association results for these levels of missingness were compared to those for the complete dataset. It was concluded that ignoring individuals with missing data substantially affects the number of regions of LD detected which, in turn, could affect tagging SNPs chosen to generate haplotypes.

Chromosome Mapping↗
PubMed1999

Demonstration by fluorescence resonance energy transfer of a close association between activated MAP kinase and neurofibrillary tangles: implications for MAP kinase activation in Alzheimer disease.

Indirect evidence suggests that activation of the mitogen activated protein kinase (MAPK) cascade contributes to the hyperphosphorylation of tau found in paired helical filaments in Alzheimer disease (AD). We report colocalization of the activated form of MAPK with Ser 199/202 and Ser 396/404 phosphotau immunoreactive neurofibrillary tangles and neuritic plaques in the Alzheimer brain. Fluorescence resonance energy transfer studies (FRET) demonstrate a tight intermolecular association of activated MAPK with these phosphotau epitopes. These data support the hypothesis that activation of MAPK contributes directly to phosphorylation of tau in AD. Moreover, the stable nature of this association in postmortem human brain may suggest a stable interaction in which activated MAPK becomes tightly linked to neurofibrillary tangles.

Aged↗