title: Casein kinase 2 phosphorylation of protein kinase C and casein kinase 2 substrate in neurons (PACSIN) 1 protein regulates neuronal spine formation.
abstract: The PACSIN (protein kinase C and casein kinase 2 substrate in neurons) adapter proteins couple components of the clathrin-mediated endocytosis machinery with regulators of actin polymerization and thereby regulate the surface expression of specific receptors. The brain-specific PACSIN 1 is enriched at synapses and has been proposed to affect neuromorphogenesis and the formation and maturation of dendritic spines. In studies of how phosphorylation of PACSIN 1 contributes to neuronal function, we identified serine 358 as a specific site used by casein kinase 2 (CK2) in vitro and in vivo. Phosphorylated PACSIN 1 was found in neuronal cytosol and membrane fractions. This localization could be modulated by trophic factors such as brain-derived neurotrophic factor (BDNF). We further show that expression of a phospho-negative PACSIN 1 mutant, S358A, or inhibition of CK2 drastically reduces spine formation in neurons. We identified a novel protein complex containing the spine regulator Rac1, its GTPase-activating protein neuron-associated developmentally regulated protein (NADRIN), and PACSIN 1. CK2 phosphorylation of PACSIN 1 leads to a dissociation of the complex upon BDNF treatment and induces Rac1-dependent spine formation in dendrites of hippocampal neurons. These findings suggest that upon BDNF signaling PACSIN 1 is phosphorylated by CK2 which is essential for spine formation.
authors: Center for Biochemistry, University of Cologne, D-50931, Cologne, Germany.
authors: Sylvia
authors: S
authors: Schael
authors: Julian
authors: J
authors: Nüchel
authors: Stefan
authors: S
authors: Müller
authors: Philipp
authors: P
authors: Petermann
authors: Jan
authors: J
authors: Kormann
authors: Isabel
authors: I
authors: Pérez-Otaño
authors: Sonia Marco
authors: SM
authors: Martínez
authors: Mats
authors: M
authors: Paulsson
authors: Markus
authors: M
authors: Plomann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D003712:Dendrites; D020868:Gene Silencing; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D009154:Mutation; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002966:Clathrin; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; C114726:Pacsin1 protein, mouse; D010750:Phosphoproteins; D012694:Serine; D047390:Casein Kinase II; D011493:Protein Kinase C; D020830:rac1 GTP-Binding Protein