title: CaMKII-dependent phosphorylation of the GTPase Rem2 is required to restrict dendritic complexity.
abstract: The morphogenesis of the dendritic arbor is a critical aspect of neuronal development, ensuring that proper neural networks are formed. However, the molecular mechanisms that underlie this dendritic remodeling remain obscure. We previously established the activity-regulated GTPase Rem2 as a negative regulator of dendritic complexity. In this study, we identify a signaling pathway whereby Rem2 regulates dendritic arborization through interactions with Ca(2+)/calmodulin-dependent kinases (CaMKs) in rat hippocampal neurons. Specifically, we demonstrate that Rem2 functions downstream of CaMKII but upstream of CaMKIV in a pathway that restricts dendritic complexity. Furthermore, we show that Rem2 is a novel substrate of CaMKII and that phosphorylation of Rem2 by CaMKII regulates Rem2 function and subcellular localization. Overall, our results describe a unique signal transduction network through which Rem2 and CaMKs function to restrict dendritic complexity.
authors.affiliation: National Center for Behavioral Genomics and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Ghiretti
authors.forename: Katelyn
authors.initials: K
authors.lastname: Kenny
authors.forename: Michael T
authors.initials: MT
authors.lastname: Marr
authors.forename: Suzanne
authors.initials: S
authors.lastname: Paradis
mesh_terms: D000818:Animals; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D014162:Transfection / Q000379:methods
chemical_list: D007527:Isoenzymes; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517599:Camk1 protein, rat; C517686:Camk4 protein, rat; D020559:Monomeric GTP-Binding Proteins; C484604:Rem2 protein, rat