S100A16, a Novel Calcium-binding Protein of the EF-hand Superfamily

Abstract

S100A16 protein is a new and unique member of the EF-hand Ca2؉ -binding proteins. S100 proteins are cell-and tissue-specific and are involved in many intra-and extracellular processes through interacting with specific target proteins. In the central nervous system S100 proteins are implicated in cell proliferation, differentiation, migration, and apoptosis as well as in cognition. S100 proteins became of major interest because of their close association with brain pathologies, for example depression or Alzheimer's disease. Here we report for the first time the purification and biochemical characterization of human and mouse recombinant S100A16 proteins. Flow dialysis revealed that both homodimeric S100A16 proteins bind two Ca 2؉ ions with the C-terminal EF-hand of each subunit, the human protein exhibiting a 2-fold higher affinity. Trp fluorescence variations indicate conformational changes in the orthologous proteins upon Ca 2؉ binding, whereas formation of a hydrophobic patch, implicated in target protein recognition, only occurs in the human S100A16 protein. In situ hybridization analysis and immunohistochemistry revealed a widespread distribution in the mouse brain. Furthermore, S100A16 expression was found to be astrocyte-specific. Finally, we investigated S100A16 intracellular localization in human glioblastoma cells. The protein was found to accumulate within nucleoli and to translocate to the cytoplasm in response to Ca 2؉ stimulation.

The EF-hand Ca2+-binding protein super-family: A genome-wide analysis of gene expression patterns in the adult mouse brain

“…For 22 genes, expression and localization studies have been performed by in-situ hybridization or immunohistochemistry (numbered in column 1). 1 (Kim et al, 2014), 2 (Vasiljevic et al, 2012) 3 (Konig et al, 2003), 4 (Blazejczyk et al, 2009), 5 (Dixon et al, 1997), 6 (Bohm et al, 2008), 7 (Yang et al, 2009), 8 (Masuda et al, 2014), 9 (Saitoh et al, 1993, 10 (Xiong et al, 2004), 11 (Bhat et al, 1994), 12 (Zhang et al, 2014), 13 (Sugita et al, 2002), 14 (Kanemaru et al, 2010), 15 (Meyer, 2014), 16 (Kuwajima et al, 1992), 17 (Sah et al, 1993), 18 (Sturchler et al, 2006), 19 (Vives et al, 2003), 20 (Mulder et al, 2010), 21 (Skibinska-Kijek et al, 2009), 22 (Saitoh et al, 1994) Gene name ISH Nr The results for the 135 genes clearly expressed in the 326 brain are presented in Table 2 Abbreviations: CA1/2/3: hippocampal fields; so: stratum oriens; sp: stratum pyramidale; sr: stratum radiatum; slm: stratum lacosum moleculare; DG: dentate gyrus; sg: granule cell layer; po: polymorph layer; hf: hippocampal fissure. ISH images for 17 genes, listed in alphabetical order, and presenting a characteristic expression pattern in the hippocampus, were taken from the ABA database.…”

Functions of S100 Proteins

“…S100A16 is upregulated in several tumors [99]. It acts as a novel adipogenesis-promoting factor, having a negative impact on insulin sensitivity [100].…”

T-2 toxin induced Salmonella Typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions

“…In contrast, T-2 toxin caused a decreased expression of proteins involved in membrane functions, mitochondrial proteins and endoplasmatic reticulum (ER) related proteins, namely annexin A4, cytochrome c oxidase subunit VIIc, chain A mitochondrial F1-ATPase complexed with aurovertin B, S-transferase 3 and S100-A16. These are involved in membrane bilayer function [38], mitochondrial electron transport [39], adenosine triphosphate (ATP) production [40], the cellular defense against oxygen-free radicals [41] or Ca 2+ homeostasis, cell proliferation, migration, differentiation, apoptosis and transcription [42,43], respectively. Moreover, T-2 toxin affects the expression of cytoskeleton associated proteins.…”