Subcellular Localization of the “Classic” S100 Subunits in Vestibular End Organs of the Rat

S100 proteins are acidic low molecular weight members of a family of calcium-binding proteins that were originally identified in the nervous system [1,2], S100 proteins have since been localized to several neuronal and non-neuronal cells, including adrenal chromaffin cells and skeletal muscle cells, in addition to glial cells and neurons [3]. The two “classic” S100 proteins were given the designation α and β. Since, these two S100 proteins tended to form homoor heterodimers with each other; they were described as “subunits” of S100. Related to their apparent function, these proteins have been reported to be closely associated with cytoskeletal proteins [3]. These “classical” S100 proteins exist in three dimeric forms (S100a [αα], S100ao [αβ] and S100b [ββ]). To fit in with the current nomenclature for S100 proteins, the α subunit is referred to as S100A1 and the β subunit is now designated S100B [4]. Since their initial identification, several other S100-related proteins with high degrees of structural homology to the S100A1 and/or S100B have been identified and are included as members of the S100 family [3,4]. A large group of S100 proteins that have similarities to S100A1 are clustered on the 1q21 loci of chromosome 1 in the human [5,6] and were named according to their spatial placement on this loci. Ridenger et al. [6] have also identified a similar distribution of many of the S100 proteins on mouse chromosome 3. The gene for S100B is located on human chromosome 21 [7]. The relationship of S100 to human brain disorders is supported by the finding that there is an increase in the level of S100B in the amniotic fluid in trisomy-21 fetuses [8], the number of glial cells expressing S100B is increased in patients with trisomy 21 (Down’s syndrome) [9,10] as well as in patients with certain forms of Alzheimer’s disease [11,12] associated with similar genetic defects on chromosome 21. Most of the S100 proteins identified on human chromosome 1 have been named using S100A plus a number to identify its location on chromosome 1 (e.g., S100A1, S100A2, etc.). Some examples of these other S100 proteins include S100A2 identified in the lungs, kidney [4] and cartilage [13], S100A4, A6 and A10 in fibroblasts [14], and S100A7-A10 in epithelial cells [15,16]. Although the apparent typical location of S100 proteins is either plasma membrane-bound or cytoplasmic, the S100A6 protein has been localized with annexin II to the nuclear envelope of smooth muscle cells [17]. S100A6 has also been reported to be associated with subpopulation of neurons and glial cells [18].