title: Localization of Triton-insoluble cAMP-dependent kinase type RIbeta in rat and mouse brain.
abstract: In eukaryotic cells, cAMP regulates many different cellular functions. Its effects are in most cases mediated by cAMP-dependent protein kinases. These consist of two regulatory and two catalytic subunits. In mammals, four different isoforms of cAMP-dependent protein kinases regulatory subunits have been characterized (RIalpha and beta, RIIalpha and beta). These four isoforms show a high level of homology and slightly different biochemical properties. In addition to biochemical properties, a different anatomical distribution of the regulatory isoforms may contribute to determine the specificity of diverse cAMP effects. By immunohistochemistry, the distribution of the detergent-insoluble fraction of RIbeta isoform has been examined in rat and mouse brain. Biochemical fractionation shows that a large fraction of both RIalpha and RIbeta isoforms is bound to the cytoskeleton. RIbeta labelling can be observed only in few locations: Purkinje cells, olfactory mitral cells, lateral thalamic neurons, superior olivary complex neurons. These cell populations are involved in the so called Purkinje cell degeneration. On the other hand, RIalpha aggregates have a more widespread distribution, in brain areas involved in visceroemotional control. At the subcellular level, these two subunits show a different pattern of labelling: in most cells a sharply defined clustered labelling is observed for RIalpha isoforms, while the RIbeta isoform presents a weaker, diffuse intracytoplasmic distribution. Competition experiments point to the presence of, as yet unidentified, different and selective anchoring proteins for the two similar RIalpha and beta isoforms. It is suggested that, as is the case for structural proteins, a different supramolecular organization of similar regulatory proteins may be crucial in order to fulfill different functions.
authors.affiliation: Dipartimento di Anatomia e Fisiologia Umana, Universita' di Padova, 35131 Padova, Italy. carla.mucignat@unipd.it
authors.forename: C
authors.initials: C
authors.lastname: Mucignat-Caretta
authors.forename: A
authors.initials: A
authors.lastname: Caretta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D054753:Cyclic AMP-Dependent Protein Kinase RIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis*; D003902:Detergents / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis*; D017830:Octoxynol / Q000494:pharmacology; D000857:Olfaction Disorders / Q000201:enzymology; D009830:Olfactory Bulb / Q000201:enzymology; D009831:Olfactory Mucosa / Q000201:enzymology; D009847:Olivary Nucleus / Q000201:enzymology; D010296:Parietal Lobe / Q000201:enzymology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000032:analysis; D021122:Protein Subunits / Q000032:analysis; D011689:Purkinje Cells / Q000201:enzymology; D051381:Rats; D012995:Solubility; D013238:Stereotaxic Techniques; D013347:Subcellular Fractions / Q000201:enzymology; D013788:Thalamus / Q000201:enzymology; D019287:Zinc Sulfate / Q000633:toxicity
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D054753:Cyclic AMP-Dependent Protein Kinase RIbeta Subunit; D003902:Detergents; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C517835:Prkar1a protein, mouse; C517836:Prkar1a protein, rat; C517768:Prkar1b protein, mouse; C517769:Prkar1b protein, rat; D020033:Protein Isoforms; D021122:Protein Subunits; D019287:Zinc Sulfate; D017830:Octoxynol; D017868:Cyclic AMP-Dependent Protein Kinases