Differential localization of MAPK-activated protein kinases RSK1 and MSK1 in mouse brain

RSK1 and MSK1 are closely related members of the MAP kinase-activated kinase family and are direct substrates and effectors of the well-studied mitogen-activated protein kinases. Although extensively characterized at the biochemical level, little is known about the localization of these protein kinases in the brain. We utilized immunohistochemistry to determine the cellular and subcellular localization of RSK1 and MSK1 in the adult mouse brain. RSK1 is expressed at highest levels in cerebellum, especially in granule neurons and within neuropil of the molecular layer. RSK1 is also expressed in microglia throughout the brain. In a focal trauma model, RSK1 immunoreactivity is increased in activated microglia. RSK1 expression is also prominent in many large pyramidal neurons throughout the brain. At the subcellular level, RSK1 is highly concentrated in the golgi apparatus of both neurons and astroglia. In contrast, MSK1 is expressed at highest levels in striatal and olfactory tubercle neurons and to a lesser degree in cerebellar Purkinje cells. MSK1 is also expressed in a subset of astroglia. At the subcellular level, MSK1 is confined to the nucleus of all expressing cell types. The differential cellular and subcellular localizations of RSK1 and MSK1 suggest divergent functional roles in the brain, with RSK1 poised to regulate membrane trafficking or membrane-localized signaling, and MSK1 involved in modification of nuclear histones and transcription factors.