Cerebral expression of the alpha2-subunit of soluble guanylyl cyclase is linked to cerebral maturation and sensory pathway refinement during postnatal development

Abstract

Soluble guanylyl cylase (sGC) has been identified for being a receptor for the gaseous transmitters nitric oxide and carbon monoxide. Currently four subunits alpha1, alpha2, beta1, and beta2 have been characterized. Heterodimers of alpha and beta-subunits as well as homodimers of the beta2-subunit are known to constitute functional sGC which use GTP to form cGMP a potent signal molecule in a multitude of second messenger cascades. Since NO-cGMP signaling plays a pivotal role in neuronal development we analyzed the maturational expression pattern of the newly characterized alpha2-subunit of sGC within the brain of Wistar rats by means of RNase protection assay and immunohistochemistry. alpha2-subunit mRNA as well as immunoreactive alpha2-protein increased during postnatal cerebral development. Topographical analysis revealed a selective high expression of the alpha2-subunit in the choroid plexus and within developing sensory systems involving the olfactory and somatosensory system of the forebrain as well as parts of the auditory and visual system within the hindbrain. In cultured cortical neurons the alpha2-subunit was localized to the cell membrane, especially along neuronal processes. During the first 11 days of postnatal development several cerebral regions showed a distinct expression of the alpha2-subunit which was not paralleled by the alpha1/beta1-subunits especially within the developing thalamo-cortical circuitries of the somatosensory system. However, at later developmental stages all three subunits became more homogenously distributed among most cerebral regions, indicating that functional alpha1/beta1 and alpha2/beta1 heterodimers of sGC could be formed. Our findings indicate that the alpha2-subunit is an essential developmentally regulated constituent of cerebral sensory systems during maturation. In addition the alpha2-subunit may serve other functions than forming a functional heterodimer of sGC during the early phases of sensory pathway refinement.