Distinct cellular and subcellular distributions of the alpha and beta isoforms of Heat Shock Protein 90 in the mouse cerebral cortex.

Heat Shock Protein (HSP) 90 is a molecular chaperone that contributes to a broad range of cellular processes in nearly all tissues including the brain. HSP90 has two isoforms, namely HSP90α and HSP90β, that have highly similar amino-acid sequences and have therefore been assumed to perform redundant functions, although their roles may be distinct in certain cellular contexts. In both the developing brain and adult brain, it remains unclear whether HSP90α and HSP90β have unique functions. Here we demonstrate that these two isoforms are differentially distributed in the mouse cerebral cortex, as evidenced by immunofluorescence staining, fluorescence in situ hybridization, and single-cell RNA sequencing data. HSP90α was strongly expressed in layer 5 excitatory neurons, inhibitory neurons across all layers, and a subset of oligodendrocytes. In addition to the populations expressing HSP90α, HSP90β was strongly expressed in layer 6 neurons. Moreover, HSP90β was preferentially enriched in distal portions of neurites compared with HSP90α. These results suggest unique roles for HSP90α and HSP90β in certain cell types of the cerebral cortex.