title: Alpha/beta-tubulin are A kinase anchor proteins for type I PKA in neurons.
abstract: Expression, localization and regulation of different cAMP-dependent protein kinase A (PKA) subunits account for specificity in the intracellular cAMP/PKA signaling pathway. In Aplysia neurons, two classes of PKA (I and II) differing in their regulatory (R) subunits have been characterized. Type I is mostly soluble in the cell body, and type II enriched at the synaptic endings. Although both types are necessary for long-term changes in synaptic plasticity, their differences in cellular localization and expression suggest that they mediate distinct functions. By photoaffinity labeling studies, we previously observed a cAMP-binding 105 kDa band in extracts from Aplysia neurons as a putative third class of R subunit of PKA. Here, we have determined that the 105 kDa band is a high molecular weight complex (HMWC) containing alpha/beta-tubulin and PKA RI, but not RII. This hetero-complex is conserved in vertebrates since mouse brain extracts also contain it. The enrichment of the endogenous HMWC by subcellular fractionation and its synthesis in vitro indicate that it is mainly produced in the cytosol, and then transported to the synapses. The HMWC is functional as a cAMP-sensitive regulatory subunit of PKA since it binds catalytic subunit in the absence of cAMP. Furthermore, serotonin (5-HT) treatment, which produces long-term facilitation in neurons, induced its degradation. In mouse brain RI co-localized with tubulin in neuropils and in COS-7 cells discretely at the cell membrane. These observations suggest that the alpha/beta-tubulin anchoring type I PKA may have an important role in the formation of long-term synaptic plasticity.
authors.affiliation: Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, NY 10032, USA. tkurosu@biken.osaka-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.forename: A Iván
authors.initials: AI
authors.lastname: Hernández
authors.forename: Jason
authors.initials: J
authors.lastname: Wolk
authors.forename: Jinming
authors.initials: J
authors.lastname: Liu
authors.forename: James H
authors.initials: JH
authors.lastname: Schwartz
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000201:enzymology*; D019556:COS Cells; D002490:Central Nervous System / Q000166:cytology / Q000201:enzymology; D002522:Chlorocebus aethiops; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / Q000378:metabolism; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000378:metabolism; D054743:Cyclic AMP-Dependent Protein Kinase Type I / Q000378:metabolism*; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000201:enzymology*; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000201:enzymology*; D012377:Rodentia / Q000378:metabolism; D013045:Species Specificity; D013347:Subcellular Fractions; D014404:Tubulin / Q000378:metabolism*
chemical_list: D054758:A Kinase Anchor Proteins; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D046911:Macromolecular Substances; D014404:Tubulin; D054743:Cyclic AMP-Dependent Protein Kinase Type I