Heterogeneity of tau proteins during mouse brain development and differentiation of cultured neurons

Larcher, Jean Christophe; Boucher, Dominique; Ginzburg, Irith; Gros, François; Denoulet, Philippe

doi:10.1016/0012-1606(92)90059-p

Cited by 33 publications

(23 citation statements)

References 33 publications

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“…Another 'nicrotubule-associated protein, MAP2, has been shown to be nore stable in dendrites than in axons and neuronal cell bodies 311. A switch in tau isoform expression would be a much later vent; it is even possible that, in some neuronal systems, includng primary cultures established from foetal brain, that the xpression of mature isoforms may never occur [32]. The presence of multiple tau isoforms in PC12 cells contrasts vith the single shortest isoform present in other cell lines.…”

Section: Discussionmentioning

confidence: 99%

Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells

Smith¹,

Anderton²,

Davis³

et al. 1995

FEBS Letters

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The axonal microtubule-associated protein, tau, is thought to play an important role in axonal growth and in the establishment of neuronal polarity. In adult human brain there are six alternatively spliced tau isoforms, which have different microtubule binding afflnlties in vitro. The tubulin-tau interaction is further mod&d by phosphorylation of tau and, compared to adult brain tau, both foetal brain tau and paired helical tilament (PHF) tau, characteristic of Alzhehner's disease, are hyperphosphorylated. In vivo both the expression of tau isoforms and their phosphorylation states are developmentally regulated. In order to establish the correlation between the expression of tau isoforms and their pattern of phosphorylation, we have characterised these two features in several in vitro models of neuronal differentiation, including the human neuroblastoma cell lines, SK-N-SH, SH-SYSY and IMR32 cells, rat PC12 cells and primary rat cortical neurones. Sensitive RT-PCR analysis revealed a different complement of tau isoforms in the different cell lines and neuritogenesis was associated mainly with an increase in the overall tau protein level with no apparent phosphorylation changes. A switch in tau isoform expression occurred only at the terminal stages of neuronal development, when it may be important in reinforcing the previously established axonal cytoarchitecture.

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Section: Discussionmentioning

confidence: 99%

Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells

Smith¹,

Anderton²,

Davis³

et al. 1995

FEBS Letters

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“…Tau proteins constitute a heterogeneous family of related gene products, generated by differential splicing and posttranslational modification, that range in size from 40 to 120 kDa (17)(18)(19)(20)(21)(22). Similar to many of their relatives in the MAP family, tau proteins are characterized by a series of small, homologous 18-amino acid repeats required for binding to tubulin, separated by 13-14 amino acid linking sequences (11).…”

Section: Resultsmentioning

confidence: 99%

Tau-beta-galactosidase, an axon-targeted fusion protein.

Callahan

Thomas²

1994

Proc. Natl. Acad. Sci. U.S.A.

154

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The most commonly used enzymatic reporter molecule, Escheichia col (-galactosidase (.3gal; -D-galactoside galactohydrolase, EC 3.2.1.23), fails to readily diuse into axons; consequently, the morphologies of «-gal-labeled neurons cannot directly be determined. For analysis of neuronal pathfinding and synaptic connectivity, this information is essential. We have constructed an axon-targeted 1-gal reporter by fusing the cDNA encoding the bovine microtubule-binding protein, tau, to lacZ, the E. In this report, we use promoter fusions to show that the tau-(-gal fusion gene product is indeed efficiently targeted to axonal processes, permitting the tracing of neuronal projections. Additionally, we present a set of useful markers generated in an enhancer-trap screen by using the bovine tau cDNA-lacZ fusion gene.During development, neurons become synaptically interconnected in a highly precise fashion. Identifying the mechanisms that underlie this specificity requires a detailed understanding of both the pathway choices made by developing neurons as they grow to their synaptic target areas and the behavior of neurons during final target selection. For most nervous systems, such studies require either the use of diffusible dyes to label specific neurons or antibodies that specifically label the entire structure of the relevant neurons throughout development (1-5). Dye-labeling requires the neurons of interest to be easily identified and, in the case of soluble dyes, penetrable with microelectrodes. This is often not feasible because of the small size of many neurons and their inaccessible locations within the nervous system. This limitation, in addition to the limited number of suitable antibody probes, has prevented the detailed analysis ofall but a few central nervous system (CNS) neurons.In Drosophila, where genetic analyses can be brought to bear on questions of neuronal development, the most efficient means to generate cell-specific markers is by enhancer trapping. In this method, a transposable P element containing the Escherichia coli lacZ gene fused to a minimal promoter is mobilized within the Drosophila genome. When this construct inserts near a gene, the minimal promoter often comes under the control of neighboring transcriptional enhancers and, as a result, directs the expression of the lacZ reporter in a pattern reflecting all or a portion of the transcriptional activity of the nearby gene. The vast majority of enhancertrap experiments have used a lacZ reporter encoding either a nuclear-targeted or a cytoplasmic form of (3-galactosidase ((3-gal; (3D-galactoside galactohydrolase, EC 3.2.1.23) (6-8). Unfortunately, neither of these forms of (-gal readily diffuses MATERIALS AND METHODSConstruction of pCftz/tau-lacZ and petau-lacZ. Standard methods were used to construct all plasmids (10). The tau cDNA-lacZ fusion gene was constructed by a three-way ligation of (i) a 1.2-kb HindIII-Rsa I fragment from pBT43-12, a bovine tau cDNA (11); (ii) a 4.2-kb Xma I-EcoRI fragment of cosPwhite (-gal (12) with the ...

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“…As phospho-isoforms of tau differ with respect to both electrophoretic mobility and pI, they can be separated on SDS-PAGE and by isoelectric focusing [4]. By 2D gel analysis as many as 60 different isoforms have been detected in adult mouse brain [10]. In the present study, the distribution of molecular isoforms and the contribution of phosphorylation to their molecular heterogeneity was studied in the soluble tau fraction of grey and white matter of temporal cortex.…”

Section: Introductionmentioning

confidence: 91%

Distribution of isoforms of the microtubule‐associated protein tau in grey and white matter areas of human brain: A two‐dimensional gelelectrophoretic analysis

et al. 1996

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The microtubule-associated protein tau in human brain consists of six molecular isoforms derived from a single gene by alternative mRNA-splicing and further modified by posttranslational processing. In the present study, the distribution of tau isoforms in grey and white matter of human temporal cortex was investigated by two-dimensional gelelectrophoresis. More than 80 isoforms were detected. The pattern of isoforms obtained after treatment with alkaline phosphatase was still more complex than those of recombinant tau, indicating that posttranslational modifications other than phosphorylation contribute to the molecular heterogeneity of tau. The tau isoform D according to Goedert [I] containing four tubulin-binding regions shown to promote tubulin polymerisation most efficiently was present in higher amounts in white as compared to grey matter. The pattern of isoform distribution was not significantly altered in Alzheimer's disease. It is concluded that molecular isoforms that differ in their tubulin-binding characteristics are differentially distributed in subceliular neuronal compartments and/or neuronal types.

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Heterogeneity of tau proteins during mouse brain development and differentiation of cultured neurons

Cited by 33 publications

References 33 publications

Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells

Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells

Tau-beta-galactosidase, an axon-targeted fusion protein.

Distribution of isoforms of the microtubule‐associated protein tau in grey and white matter areas of human brain: A two‐dimensional gelelectrophoretic analysis

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