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Introduction Stable tubule-only polypeptide (STOP) proteins are a family of calmodulin binding and regulated microtubule associated proteins (MAPs), encoded by a single gene (mouse (Mtap6), Denarier et al., 1998b; human [...], Stable tubule-only polypeptide (STOP) proteins are a family of microtubule associated proteins (MAPs) important in microtubule stabilization. Data indicating a role for microtubules in synaptic function has come from studies of the STOP null mouse, which exhibits synaptic deficits, in association with behavioural changes that are alleviated by antipsychotic treatment. These findings suggested that STOP mutant mice may be useful in studies of synaptic function, and could be especially relevant to schizophrenia, postulated to be a disorder of the synapse. Moreover, a genetic association between STOP and schizophrenia has been reported. This study aimed to further characterize synaptic alterations in STOP null and heterozygous mice. Using in situ hybridization histochemistry, the mRNA expression of three pre-synaptic (synaptophysin; growth associated protein-43 (GAP-43); vesicular glutamate transporter-1 (VGlut1)) and two post-synaptic (spinophilin; MAP2) proteins, was quantified in female STOP null (n = 7), heterozygous (n = 5) and wild type (n = 6) mice. For STOP null and heterozygous mice, synaptophysin, VGlut1, GAP-43 and spinophilin mRNAs were decreased in the hippocampus, whilst in addition in the null mice, synaptophysin, VGlut1 and spinophilin mRNAs were decreased in the cerebellum. Alterations in synaptic protein mRNA expression were also detected in the frontal and occipital cortex. MAP2 mRNA expression was unchanged in all brain regions. The profile of mRNA changes is broadly similar to that observed in schizophrenia. Together the data provide supporting evidence for a role for microtubules in synaptic function, and suggest that STOP, or other microtubule proteins, may contribute to the synaptic pathology of schizophrenia. Key words in situ hybridization histochemistry, MAP6, microtubules, mRNA, MAP2) proteins, was quanti?ed in female STOP null (n =7), heterozygous schizophrenia, synapse

There are six distinct tubulin binding sites on gamma-tubulin and they are clustered in the central region of the primary amino acid sequence. In the tertiary structure, these sites occur on both sides of the molecule.

A study was conducted to analyze the dissociation of tubulin heterodimers into separate alpha and beta-tubulin subunits using an immunoaffinity framework. Phosphocellulose column chromatography was carried out to purify tubulin from bovine brain. Results indicated the need for an intact heterodimer during the binding of colchicine with tubulin. Findings also showed that tubulin loses its colchicine binding capacity after dissociation to monomers.

The interaction of centrosome with free tubulin dimers was investigated by fluorescence microscopic examination of cultured cells which have been lysed, supplemented with semiquantitative binding assays. The results revealed that the centrosomes specifically accumulate tubulin dimers through their tubulin binding sites which number to about 25000. Such binding sites are thought to be distinct from the gamma-tubulin itself and appear to be important in the kinetics of tubulin nucleation on centrosomes.

The distribution of tubulin variants in the axonemial microtubules of sea urchin sperm flagella, is studied by immunological processes and by direct sequence and mass spectrometric analysis of the carboxy-terminal peptides. The A and B tubules that comprise the nine outer doublets have very different tubulin variants. A tubules are composed of more than 95% unmodified, tyrosinated alpha-beta-tubulin. In B tubules, alpha-tubulin is about 65% detyrosinated and both alpha- and beta-tubulin are 40-45% polyglycylated.

The 34K protein is crucial to the functioning of microtubules in eukaryotes. Microtubules are important parts of the cilia and flagella found in eukaryotic cells. Research involving the sea urchin species Paracentrotus lividus showed that 34K, which has the same structure as the nuclear histone H1, helps the microtubules to achieve the molecular stability necessary for cilia and flagella to grow. The improved understanding of microtubule stabilization may provide evidence for how the eukaryotes evolved from the prokaryotes.

The stable tubule only polypeptide (STOP)-like effectors, which stabilizes microtubules, in bovine brain were studied. The activity of bovine brain supernatants binds to cation exchangers and Ca2+-calmodulin affinity columns. Two distinct activities were found. Analysis of the 220-kDa protein show that it is the bovine equivalent of the rat brain STOP145. Meanwhile, the 20-kDa polypeptide is believed to be the myelin basic protein (MBP). Moreover, the results suggest that MBP and STOPs stabilize microtubules in a similar manner but in different cell types.

Resistance of microtubules to the cold is largely due to polymer association with a class of microtubule-associated proteins called stable tubule only polypeptides (STOPs). Importance of STOPs for synaptic plasticity is discussed along with the disorders induced by their suppression in whole animals.