title: Association of the type 1 inositol (1,4,5)-trisphosphate receptor with 4.1N protein in neurons.
abstract: The type 1 inositol (1,4,5)-trisphosphate receptor (InsP(3)R1) is an intracellular calcium (Ca(2+)) release channel that plays an important role in neuronal function. In yeast two-hybrid screen of rat brain cDNA library with the InsP(3)R1 carboxy-terminal bait we isolated multiple clones of neuronal cytoskeletal protein 4.1N. We mapped the 4.1N-interaction site to a short fragment (50 amino acids) within the carboxy-terminal tail of the InsP(3)R1 and the InsP(3)R1-interaction site to the carboxy-terminal domain (CTD) of 4.1N. We established that InsP(3)R1 carboxy-terminal binds selectively to the CTDDelta alternatively spliced form of the 4.1N protein. In biochemical experiments we demonstrated that 4.1N and InsP(3)R1 specifically associate in vitro. We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. In biochemical experiments we demonstrated a possibility of InsP(3)R1-4.1N-CASK-syndecan-2 quaternary complex formation. From our findings we hypothesize that InsP(3)R1-4.1N association may play a role in InsP(3)R1 localization or Ca(2+) signaling in neurons.
authors.affiliation: Department of Physiology, UT Southwestern Medical Center at Dallas, 75390, Dallas, TX, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Maximov
authors.forename: Tie Shan
authors.initials: TS
authors.lastname: Tang
authors.forename: Ilya
authors.initials: I
authors.lastname: Bezprozvanny
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D053669:Syndecan-2; D020798:Two-Hybrid System Techniques
chemical_list: D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009479:Neuropeptides; D011509:Proteoglycans; D018160:Receptors, Cytoplasmic and Nuclear; C508247:Sdc2 protein, rat; C120557:erythrocyte membrane protein band 4.1-like 1; D053669:Syndecan-2; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; D002118:Calcium