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Specific interaction of TSC22D4 forms with chromatin, mAIF and nuclear matrix in differentiated and apoptosis committed-cerebellar granule neurons
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Opposite Roles Of Tgf-ß1-Responsive Tsc22d Proteins In Regulating Cerebellar Granule Neurons Differentiation And Commitment To Apoptosis
No full textThe TSC22D (Transforming Growth Factor ß1-stimulated clone 22 domain) protein family includes widely expressed members having a TSC box and a leucine zipper domain and controlling multiple biological processes. Among these members, TSC22D4 is involved in cerebellum granule neuron (CGN) differentiation and commitment to apoptosis.
These opposite functions rely on the existence of multiple TSC22D4 forms differing in modification, subcellular localization and function. In contrast to 42 kDa and 55 kDa forms, 67 kDa and 72 kDa forms have specific posttranslational modifications and subcellular localizations: the 67 kDa form is O-GlcNAcylated and unphosphorylated, whereas the 72 kDa form is O-GlcNAcylated and phoshorylated. Moreover, while the latter form is associated with chromatin, the 67 kDa form is associated with Apoptosis Inducing Factor (AIF) in mitochondria under normal cell viability conditions. However, when CGNs are committed to apoptosis the 67 kDa form is rapidly transferred from mitochondria to nuclear matrix with a kinetics similar to that of AIF transfer from mitochondria to chromatin, suggesting that the mitochondrial release of AIF and TSC22D4 is triggered by a regulatory mechanism(s) acting upon the entire AIF-TSC22D4 complex.
Besides Tsc22d4, CGNs also express Tsc22d1, the first identified member of TSC22D family, which is in turn expressed with two splice variants encoding TSC22D1-1 and TSC22D1-2 proteins.
While TSC22D1-2 is consistently expressed during CGN differentiation, TSC22D1-1 is highly expressed in undifferentiated CGNs and barely detected in fully differentiated CGNs. CGN apoptosis commitment triggers TSC22D1-1 translocation from the nucleus to the cytoplasm but does not modifies the nucleo/cytoplasmic distribution of TSC22D1-2. By immunoprecipitation experiments we have found that both TSC22D1-1 and TSC22D1-2 interact with TSC22D4 and that TSC22D1-1 also interacts with large conductance Ca+2-activated K+ channels (BKCa). Our findings on TSC22D4 and TSC22D1 subcellular localization/interacting protein partners depending on CGN differentiation/functional condition will be presented
The tumor suppressor TSC22D4 and AIF associate in mitochondria and shift to different nuclear compartments at the onset of apoptosis
No full textSubcellular TSC22D4 localization in cerebellum granule neurons of the mouse depends on development and differentiation
No full textWe previously demonstrated that TSC22D4, a protein encoded by the TGF-beta 1-activated gene Tsc22d4 (Thg-1pit) and highly expressed in postnatal and adult mouse cerebellum with multiple post-translationally modified protein forms, moves to nucleus when in vitro differentiated cerebellum granule neurons (CGNs) are committed to apoptosis by hyperpolarizing KCl concentrations in the culture medium. We have now studied TSC22D4 cytoplasmic/nuclear localization in CGNs and Purkinje cells: (1) during CGN differentiation/maturation in vivo, (2) during CGN differentiation in vitro, and (3) by in vitro culturing ex vivo cerebellum slices under conditions favoring/inhibiting CGN/Purkinje cell differentiation. We show that TSC22D4 displays both nuclear and cytoplasmic localizations in undifferentiated, early postnatal cerebellum CGNs, irrespectively of CGN proliferation/migration from external to internal granule cell layer, and that it specifically accumulates in the somatodendritic and synaptic compartments when CGNs mature, as indicated by TSC22D4 abundance at the level of adult cerebellum glomeruli and apparent lack in CGN nuclei. These features were also observed in cerebellum slices cultured in vitro under conditions favoring/inhibiting CGN/Purkinje cell differentiation. In vitro TSC22D4 silencing with siRNAs blocked CGN differentiation and inhibited neurite elongation in N1E-115 neuroblastoma cells, pinpointing the relevance of this protein to CGN differentiation
Multiple TSC22D4 iso-/phospho-glycoforms display idiosyncratic subcellular localizations and interacting protein partners
No full textProteins of the TSC22 domain (TSC22D) family, including TSC22D1 and TSC22D4, play pivotal roles in cell proliferation, differentiation and apoptosis, interacting with other factors in a still largely unknown manner. This study explores this issue by biochemically characterizing various TSC22D4 forms (both iso- and glyco-phospho-, namely the splice variants 42 and 55 kDa and the post-translationally modified 67 and 72 kDa forms) and their subcellular localization and protein partners during cerebellar granule neuron (CGN) differentiation. The TSC22D4-42 form is mostly cytosolic, and is the only TSC22D4 form that associates with TSC22D1.2 in undifferentiated but not differentiated CGNs. In contrast, TSC22D4-55 is prominently associated with the nuclear matrix in differentiated but not undifferentiated CGNs. As for TSC22D4-67, it is localized in the cytosol and nuclei of undifferentiated CGNs and enters mitochondria of differentiated CGNs, associating with apoptosis-inducing factor. TSC22D4-72 is modified by O-linked beta-N-acetylglucosamine (O-GlcNAcylated) and phosphorylated and is always associated with chromatin irrespective of CGN differentiation. The various subcellular localization patterns and interacting protein partners of TSC22D4 forms during CGN differentiation suggest the existence of form-specific function(s) and provide a novel framework to further investigate the biological functions of TSC22D proteins. Structured digital abstract AIF and TSC22D4 colocalize by cosedimentation (View interaction). TSC22D1 physically interacts with TSC22D4 by anti bait coimmunoprecipitation (View Interaction: 1, 2). TSC22D4 physically interacts with AIF by anti bait coimmunoprecipitation (View Interaction: 1, 2). AIF and TSC22D4 colocalize by cosedimentation (View interaction). Proteins of TSC22 domain family play isoform-specific roles in cell proliferation, differentiation and apoptosis. We have characterized the nature, subcellular localizations and protein partners of TSC22D4 splice variants TSC22D4-42 and TSC22D4-55 and glyco-phospho-forms TSC22D4-67 and TSC22D4-72. TSC22D4-42 and TSC22D4-67 associate with TSC22D1.2 and mitochondrial AIF, respectively, depending on neuronal differentiation. TSC22D4-72 and TSC22D4-55 are stably chromatin- and nuclear matrix-associated, respectively © 2013 FEBS
Specific interaction of TSC22D4 forms with chromatin, mitochondrial apoptosis inducing factor and nuclear matrix in differentiated and apoptosis-committed cerebellar granule neurons.
No full textTSC22D1 regulates cerebellum granule neurons differentiation by interacting with TSC22D4 and BKCa potassium channels.
No full textSex effect on presenilins expression in post-natal rat brain
No full textPresenilin 1 and presenilin 2 are widely expressed during brain development. Several mutations in these proteins have been associated with autosomal-domi- nant inherited forms of Alzheimer disease. Their ex- pression is regulated by various cellular and ex- tracellular factors, which change with age and sex. Both age and sex are key risk factors for Alzheimer’s disease, but the issue of whether the expression of presenilins is influenced by the sex during early post- natal development of the brain has been poorly inves- tigated so far. In this study, we report that transcript levels of presenilins, and the subset of neurons ex- pressing these proteins in various brain areas of the developing post-natal brain are different in male and female rats, suggesting that their function(s) may contribute to sexual dimorphism in the brain, both at morphological and functional level
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