title: Identification of kalirin-7 as a potential post-synaptic density signaling hub.
abstract: Kalirin-7 (Kal7), a multifunctional Rho GDP/GTP exchange factor (GEF) for Rac1 and RhoG, is embedded in the postsynaptic density at excitatory synapses, where it participates in the formation and maintenance of dendritic spines. Kal7 has been implicated in long-term potentiation, fear memories, and addiction-like behaviors. Using liquid chromatography and tandem mass spectroscopy, we identified sites phosphorylated by six PSD-localized kinases implicated in synaptic plasticity and behavior, sites phosphorylated when myc-Kal7 was expressed in non-neuronal cells and sites phosphorylated in mouse brain Kal7. A site in the Sec14p domain phosphorylated by calcium/calmodulin dependent protein kinase II, protein kinase A and protein kinase C, was phosphorylated in mouse brain but not in non-neuronal cells. Phosphorylation in the spectrin-like repeat region was more extensive in mouse brain than in non-neuronal cells, with a total of 20 sites identified. Sites in the pleckstrin homology domain and in the linker region connecting the GEF domain to the PDZ binding motif were heavily phosphorylated in both non-neuronal cells and in mouse brain and affected GEF activity. We postulate that the kinase convergence and divergence observed in Kal7 identify it as a key player in integration of the multiple inputs that regulate synaptic structure and function.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
authors.forename: Drew D
authors.initials: DD
authors.lastname: Kiraly
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Stone
authors.forename: Chris M
authors.initials: CM
authors.lastname: Colangelo
authors.forename: Tom
authors.initials: T
authors.lastname: Abbott
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Richard E
authors.initials: RE
authors.lastname: Mains
authors.forename: Betty A
authors.initials: BA
authors.lastname: Eipper
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000737:chemistry; D010766:Phosphorylation; D057907:Post-Synaptic Density / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission; D053719:Tandem Mass Spectrometry; D013912:Threonine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C548820:KALRN protein, mouse; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013912:Threonine; D017346:Protein Serine-Threonine Kinases