α/β-tubulin are A kinase anchor proteins for type I PKA in neurons

• Published in: Brain research Vol. 1251; pp. 53 - 64
• Main Authors: Kurosu, Takeshi, Hernández, A. Iván, Wolk, Jason, Liu, Jinming, Schwartz, James H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.01.2009; Elsevier
• Subjects: A Kinase Anchor Proteins - metabolism; AKAP; Animals; Aplysia; Aplysia - cytology; Aplysia - enzymology; Biochemistry. Physiology. Immunology; Biological and medical sciences; Central Nervous System - cytology; Central Nervous System - enzymology; Cercopithecus aethiops; COS Cells; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit - metabolism; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit - metabolism; Cyclic AMP-Dependent Protein Kinase Type I - metabolism; Fundamental and applied biological sciences. Psychology; Ganglia, Invertebrate - cytology; Ganglia, Invertebrate - enzymology; Invertebrates; Macromolecular Substances - chemistry; Macromolecular Substances - metabolism; Mice; Molecular Weight; Mollusca; Neurology; Neuron; Neuronal Plasticity - physiology; Neurons - enzymology; Physiology. Development; PKA; Rodentia - metabolism; Species Specificity; Subcellular Fractions; Synapse; Tubulin; Tubulin - metabolism; HMWC; Aplysia; serotonin; Synapse; Tubulin; Neuron; AKAP; PKA; 5-HT; a high molecular weight complex; A kinase-anchoring protein; Enzyme; Transferases; Non-specific serine/threonine protein kinase; Gastropoda; Invertebrata; Mollusca
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.11.019

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 α/β-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 α/β-tubulin anchoring type I PKA may have an important role in the formation of long-term synaptic plasticity.