S100A6 and its binding partners in nervous system
S100A6 is an EF-hand calcium binding protein belonging to the S100 family (Lesniak et al. 2009). In the Ca2+-bound form S100A6 is able to interact with several ligands. More recent discoveries concerning S100A6 targets showed that it is able to form complexes with CacyBP/SIP or Sgt1. Since expression of these two S100A6 targets in brain is very high our work was focused on elucidating the role of CacyBP/SIP and Sgt1 in brain tissue. Immunohistochemistry performed on rat brain slices revealed that CacyBP/SIP is present in neurons of the cerebellum, hippocampus and cortex (Jastrzebska et al. 2000). Analysis of CacyBP/SIP mRNA expression during rat brain development showed its highest level in the cerebellum at postnatal day 21st. This might suggest the involvement of CacyBP/SIP in development of rat brain. We also examined localization of CacyBP/SIP in cultured neurons and in brain neurons of young and aged rats (Filipek et al. 2008). The results indicate that in neurons of young rats CacyBP/SIP localization is different than in aged animals. Moreover, we found that localization of CacyBP/SIP in brain neurons is similar to that observed for tau and tubulin suggesting its involvement in cytoskeletal physiology. Regarding Sgt1, we observed its immunostaining in Purkinje cells of the cerebellum, in granule cells of the dentate gyrus of the hippocampus and in multiple neurons of the cortex (Spiechowicz et al. 2006). We also compared the density of Sgt1-immunopositive neurons in cortical layers of brain sections derived from healthy aged and AD-affected individuals. We found a significant decrease in Sgt1-immunopositive neurons in the temporal, angular and posterior cingulate cortex of AD brains. Such diminished immunostaining in AD cortex points to Sgt1 as a possible marker of degenerating neurons. This work was supported by grant N N303 548439 from the Ministry of Science and Higher Education of Poland to A.F. and by statutory funds from the Nencki Institute.
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