Immunoreactive forms of erythrocyte spectrin and ankyrin in brain

1982 ◽  
Vol 299 (1095) ◽  
pp. 301-312 ◽  
Keyword(s):  
Molecular Mass ◽  
Erythrocyte Membranes ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
Molecular Masses ◽  
Low Ionic Strength ◽  
Polypeptide Chains ◽  
The Brain ◽  
Total Membrane ◽  
Rotary Shadowing

Polypeptides immunologically related to erythrocyte spectrin and ankyrin have been detected in brain. The cross-reacting proteins include soluble as well as membrane-associated forms. A class of soluble cross-reacting polypeptides have been identified as high molecular mass microtubule-associated proteins (MAPS). MAP1, a group of polypeptides of molecular mass ca . 370 kDa contains a component that cross-reacts with anti-ankyrin IgG. MAP2, a polypeptide of molecular mass 300 kDa cross-reacts with anti-spectrin IgG, with the shared antigenic sites localized to the α chain of spectrin. The functional basis for structural homology between MAP1 and ankyrin may involve association with tubulin, since erythrocyte ankyrin binds to microtubules polymerized from pure brain tubulin. Spectrin did not associate with microtubules, but does have in common with MAP2 the ability to bind to actin (Brenner & Korn 1979; Sattilaro et al . 1981) and the shape of a flexible rod as visualized by rotary shadowing (Shotton et al . 1979; Voter & Erickson 1981). Immunoreactive forms of spectrin and ankyrin are also present in membrane fractions. A homologue of spectrin which constitutes 3% of the total membrane protein has been purified from low ionic strength extracts of membranes. This protein contains two non-identical polypeptide chains of molecular masses of 260 and 265 kDa, binds to F-actin, and displaces binding of erythrocyte spectrin to erythrocyte membranes. The brain protein pas been visualized by rotary shadowing as an extended rod-like molecule 195 nm in length. These studies indicate that the organization of proteins in the membrane-cytoskeleton complex of erythrocytes has direct relevance to other types of cells, and suggest the existence of families of proteins related to spectrin and ankyrin.

scholarly journals Exploring neurodegeneration at the atomic level

2018 ◽  
Vol 40 (5) ◽  
pp. 9-11
Author(s):  
Adam Tozer
Keyword(s):  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Atomic Level ◽  
Tau Proteins ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Central Nervous System ◽  
The Brain ◽  
Cell Maintenance

Tau proteins are microtubule-associated proteins essential for the correct functioning of neurons. This small family of proteins, 352–441 amino acids in length, are abundant in the brain and exist to stabilize microtubules in neurons and glia (non-neuronal cells of the central nervous system) to ensure correct trafficking of cellular cargo and cell maintenance.

scholarly journals Identification of disease-relevant modulators of the SHH pathway in the developing brain

Development ◽  
2021 ◽  
Vol 148 (17) ◽  
Author(s):  
Nora Mecklenburg ◽  
Izabela Kowalczyk ◽  
Franziska Witte ◽  
Jessica Görne ◽  
Alena Laier ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Modifier Genes ◽  
Microtubule Associated Proteins ◽  
Shh Pathway ◽  
Brain Malformations ◽  
Associated Proteins ◽  
Positive Regulators ◽  
Functional Analyses ◽  
The Brain ◽  
Variable Penetrance

ABSTRACT Pathogenic gene variants in humans that affect the sonic hedgehog (SHH) pathway lead to severe brain malformations with variable penetrance due to unknown modifier genes. To identify such modifiers, we established novel congenic mouse models. LRP2-deficient C57BL/6N mice suffer from heart outflow tract defects and holoprosencephaly caused by impaired SHH activity. These defects are fully rescued on a FVB/N background, indicating a strong influence of modifier genes. Applying comparative transcriptomics, we identified Pttg1 and Ulk4 as candidate modifiers upregulated in the rescue strain. Functional analyses showed that ULK4 and PTTG1, both microtubule-associated proteins, are positive regulators of SHH signaling, rendering the pathway more resilient to disturbances. In addition, we characterized ULK4 and PTTG1 as previously unidentified components of primary cilia in the neuroepithelium. The identification of genes that powerfully modulate the penetrance of genetic disturbances affecting the brain and heart is likely relevant to understanding the variability in human congenital disorders.

A high molecular mass phosphoprotein defined by a novel monoclonal antibody is closely associated with the intermicrotubule cross bridges in the Trypanosoma brucei cytoskeleton

1992 ◽  
Vol 103 (3) ◽  
pp. 665-675 ◽  
Author(s):  
A. Woods ◽  
A.J. Baines ◽  
K. Gull
Keyword(s):  
Molecular Mass ◽  
Trypanosoma Brucei ◽  
Minor Component ◽  
Relative Molecular Mass ◽  
Microtubule Associated Proteins ◽  
Heat Stable ◽  
Cytoplasmic Face ◽  
Associated Proteins ◽  
Cross Bridges ◽  
Main Component

The main component of the cell body cytoskeleton of Trypanosoma brucei is the highly organised array of stable, subpellicular microtubules on the cytoplasmic face of the plasma membrane. Although several microtubule associated proteins (MAPs) have been shown to be associated with this array, the mechanisms by which individual microtubules interact with one another and with the membrane are still largely undetermined. In this study we have used the T. brucei cytoskeleton as a complex immunogen for the production of monoclonal antibodies to define novel cytoskeletal antigens. Screening by immunofluorescence enabled the selection of an antibody, WCB-1, which detects an antigen associated specifically with the subpellicular microtubules and not with the flagellum microtubules. The antigen (WCB210) was shown to have a relative molecular mass of 210,000 by western blotting. Immunogold studies showed the epitope to be located on the membrane-facing side of the subpellicular cage; it appears to be closely associated with the cross-bridges lying between the microtubules. Unlike many MAPs this protein was shown not to be heat stable and is predicted to be a roughly globular monomer. Even though WCB210 is a very minor component of the cytoskeleton it is heavily phosphorylated. It is possible that this protein is involved in regulation of the subpellicular microtubule crossbridges by interaction with other proteins.

Identification of SV40 large T-antigen-associated proteins in cardiomyocytes from transgenic mice

1993 ◽  
Vol 264 (5) ◽  
pp. H1693-H1700 ◽  
Author(s):  
A. I. Daud ◽  
N. A. Lanson ◽  
W. C. Claycomb ◽  
L. J. Field
Keyword(s):  
Transgenic Mice ◽  
Molecular Mass ◽  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
Cellular Targets ◽  
P53 Antibodies ◽  
Associated Proteins ◽  
A Cell ◽  
Molecular Masses

A cell line derived from transgenic mice expressing the SV40 large T-antigen oncogene in the heart was used to identify cardiomyocyte targets for T-antigen binding. A novel protein of molecular mass of 193 kDa was identified as an associated protein by virtue of its ability to be co-immunoprecipitated with multiple anti-T-antigen antibodies. Two previously described proteins, p120 and p53, were also observed to complex with T-antigen in transformed cardiomyocytes. In addition, several proteins that cross-reacted with either anti-T-antigen or anti-p53 antibodies were identified. Two of these proteins, of apparent molecular masses of 250 and 110 kDa, were only observed in cardiomyocytes. Expression of a third cross-reacting protein of a molecular mass of 180 kDa appeared to be dependent on the growth status of the cells. These proteins may be important constituents of the cardiomyocyte cell cycle, as well as potential cellular targets for myocardial regeneration.

scholarly journals Map1b Is Required for Axon Guidance and Is Involved in the Development of the Central and Peripheral Nervous System

2000 ◽  
Vol 151 (6) ◽  
pp. 1169-1178 ◽  
Author(s):  
Arabella Meixner ◽  
Silke Haverkamp ◽  
Heinz Wässle ◽  
Susanne Führer ◽  
Johann Thalhammer ◽  
...  
Keyword(s):  
Nervous System ◽  
Nerve Conduction Velocity ◽  
Developmental Defect ◽  
Myelinated Fiber ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
And Function ◽  
The Brain ◽  
Deficient Mice

Microtubule-associated proteins such as MAP1B have long been suspected to play an important role in neuronal differentiation, but proof has been lacking. Previous MAP1B gene targeting studies yielded contradictory and inconclusive results and did not reveal MAP1B function. In contrast to two earlier efforts, we now describe generation of a complete MAP1B null allele. Mice heterozygous for this MAP1B deletion were not affected. Homozygous mutants were viable but displayed a striking developmental defect in the brain, the selective absence of the corpus callosum, and the concomitant formation of myelinated fiber bundles consisting of misguided cortical axons. In addition, peripheral nerves of MAP1B-deficient mice had a reduced number of large myelinated axons. The myelin sheaths of the remaining axons were of reduced thickness, resulting in a decrease of nerve conduction velocity in the adult sciatic nerve. On the other hand, the anticipated involvement of MAP1B in retinal development and γ-aminobutyric acid C receptor clustering was not substantiated. Our results demonstrate an essential role of MAP1B in development and function of the nervous system and resolve a previous controversy over its importance.

Unusual properties of a cold-labile fraction of Atlantic cod (Gadus morhua) brain microtubules

1989 ◽  
Vol 67 (11-12) ◽  
pp. 791-800 ◽  
Author(s):  
E. Strömberg ◽  
L. Serrano ◽  
J. Avila ◽  
M. Wallin
Keyword(s):  
Molecular Mass ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Bovine Brain ◽  
Microtubule Assembly ◽  
Microtubule Associated Proteins ◽  
Heat Stable ◽  
Labile Fraction ◽  
Associated Proteins ◽  
Brain Microtubules

A cold-labile fraction of microtubules with unusual properties was isolated from the brain of the Atlantic cod (Gadus morhua). The yield was low, approximately six times lower than that for bovine brain microtubules. This was mainly caused by the presence of a large amount of cold-stable microtubules, which were not broken down during the disassembly step in the temperature-dependent assembly–disassembly isolation procedure and were therefore lost. The isolated cold-labile cod microtubules contained usually only a low amount of microtubule-associated proteins (MAPs). Three high molecular mass proteins were found, of which one was recognized as MAP2. Cod MAP2 differed from mammalian brain MAP2; it was not heat stable and had a slightly higher molecular mass. In contrast to mammalian MAPs, MAP1 was not found in the cold-labile fraction of microtubules. A new heat-labile MAP of higher molecular mass (400 kilodaltons) was however present, as well as a heat-stable protein of slightly lower molecular mass than MAP2. These MAPs showed similar tubulin-binding characteristics as bovine brain MAPs, since they coassembled with taxol-assembled bovine brain microtubules consisting of pure bovine tubulin. In spite of the fact that Ca2+ bound equally to cod and porcine tubulins, it did not inhibit cod microtubule assembly even at high concentrations (> 1 mM). In contrast, rings, spirals, and macrotubules were formed. The results show that there are major differences between this fraction of cod microtubules and microtubules from mammalian brain.Key words: microtubules, microtubule-associated proteins, calcium, cod.

scholarly journals Tau in Health and Neurodegenerative Diseases

2021 ◽  
Author(s):  
Dandan Chu ◽  
Fei Liu
Keyword(s):  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Dynamic Properties ◽  
Corticobasal Degeneration ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
Argyrophilic Grain ◽  
The Brain ◽  
Filamentous Inclusions

Tau, one of the major microtubule-associated proteins, modulates the dynamic properties of microtubules in the mammalian nervous system. Tau is abundantly expressed in the brain, particularly in the hippocampus. Insoluble and filamentous inclusions of tau in neurons or glia are discovered in neurodegenerative diseases termed ‘tauopathies’, including Alzheimer’s disease (AD), argyrophilic grain disease (AGD), corticobasal degeneration (CBD), frontotemporal dementia (FTD), Pick’s disease (PiD) and progressive supranuclear palsy (PSP). Accumulation of intracellular neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau, is directly correlated with the degree of Alzheimer\'s dementia. This chapter reviews the role of tau protein in physiological conditions and the pathological changes of tau related to neurodegenerative diseases. The applications of tau as a therapeutic target are also discussed.

scholarly journals Identification of novel disease relevant genetic modifiers affecting the SHH pathway in the developing brain

2020 ◽  
Author(s):  
Nora Mecklenburg ◽  
Izabela Kowalczyk ◽  
Franziska Witte ◽  
Jessica Görne ◽  
Alena Laier ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Genetic Modifiers ◽  
Microtubule Associated Proteins ◽  
Shh Pathway ◽  
Brain Malformations ◽  
Associated Proteins ◽  
Positive Regulators ◽  
Functional Analyses ◽  
The Brain ◽  
Variable Penetrance

SUMMARYPathogenic gene variants in humans affecting the sonic hedgehog (SHH) pathway lead to severe brain malformations with variable penetrance due to unknown genetic modifiers. To identify such modifiers, we established novel congenic mouse models. LRP2 deficient C57BL/6N mice suffer from heart outflow tract defects and holoprosencephaly caused by impaired SHH activity. These defects are fully rescued on FVB/N background indicating a strong influence of modifier genes. Applying comparative transcriptomics, we identified Pttg1 and Ulk4 as candidate modifiers upregulated in the rescue strain. Functional analyses showed that ULK4 and PTTG1, both microtubule-associated proteins, are new positive regulators of SHH signaling, rendering the pathway more resilient to disturbances. In addition, we characterized PTTG1 as a novel primary cilia component in the neuroepithelium. The identification of genes, that powerfully modulate the penetrance of genetic disturbances affecting the brain and heart, is likely relevant to understand variability in human congenital disorders.

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