Our observations are in accordance with quantitative in situ hybridization where TA mRNA Diperodon signal intensity was greatest in regions with high neuronal density such as the IGL of the cerebellum. We noticed that cells belonging to the same neuronal or glial populations show a variable expression of TA. In addition, despite TA was not observed in most of the nuclei, we observed a nuclear localization in those cells which expressed high levels of TA. Several studies on TA have indicated the primary location of TA in the ER lumen where it typically forms oligomeric complexes and likely acts as a chaperone. Here, we detected the presence of a punctuate staining of TA also along dendrites, dendritic spines and axons in particular of PCs. Such distribution is in accordance with the presence of a local ER network which plays critical neuronal function. Interestingly, in dendrites and in spines the ER network allows the local translation of mRNAs encoding signal peptide-containing proteins, thus by passing the somatic ER, suggesting a role for TA in synaptic plasticity events. However, besides its localization in the ER, TA has been detected in the cytosol and in neurite processes as part of a protein complex which included cytoskeletal elements such as vimentin, actin, tubulin, and the motor protein, kinesin light chain 1. Interaction with cytoplasmic partners suggests that there may be a form of TA which has access to the cytoplasm or that, through binding to other ER-associated proteins which extend out of the ER, TA may take part in a protein complex that spans from the lumen of the ER to the cytoplasm. By interacting with the cytoskeletal network TA may contribute to control neurite outgrowth and could be involved in maintaining cell polarity. Accordingly, its developmental regulation suggests that TA may play a role in postnatal maturational events in the CNS, such as dendritic and axonal arborization. Here, we observed that TA is highly expressed in different cerebellar neurons, such as PCs and DCN. A major novel finding of the present work is the localization of TA not only in the dendritic arbor but also in the spines of developing PCs. Of note, it has been recently observed that a reduced expression of TA selectively in PCs induced alterations of PC development resulting in shortened primary dendrites and decreased spine density. Furthermore, most of the output fibers of the cerebellum originate in the DCN. Interestingly, DYT1 heterozygous knock-in mice, which carry a mutant TA, exhibited subtle WM abnormalities in cerebello-thalamo-cortical motor pathways similar to those identified in human gene carriers. Moreover, TA might be involved in the correct spatial distribution of neuron output. Accordingly, one of the best example of neuronal class-specific Sipeimine innervation patterns is found in cerebellum. In particular, PCs which reside in the translobular plane of the cerebellar cortex receive two excitatory and two inhibitory synaptic inputs impinging on well defined territories of the dendritic arbor. Importantly, in the ML the Bergmann glia cells are positioned to interact with multiple neuronal components and contribute, at different developmental stages, to multiple aspects of cerebellar circuit assembly, including spinogenesis and axon arborization. Here, we demonstrated that TA is also expressed by this cell type where it might play a role in maturation. Bergmann glia are highly polarized astrocytes, whose radial fibers dominate the cerebellar cortex. During postnatal cerebellar development, the apical Bergmann glia fibers form the earliest radial structures across the cerebellar cortex and develop characteristic endfeet at pia level.
We observed a strong presence of TA not only in the Bergmann glia cell bodies and radial
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