title: The GTPase Rem2 regulates synapse development and dendritic morphology.
abstract: Rem2 is a member of the Rad/Rem/Rem2/Gem/Kir subfamily of small Ras-like GTPases that was identified as an important mediator of synapse development. We performed a comprehensive, loss- of-function analysis of Rem2 function in cultured hippocampal neurons using RNAi to substantially decrease Rem2 protein levels. We found that knockdown of Rem2 decreases the density and maturity of dendritic spines, the primary site of excitatory synapses onto pyramidal neurons in the hippocampus. Knockdown of Rem2 also alters the gross morphology of dendritic arborizations, increasing the number of dendritic branches without altering total neurite length. Thus, Rem2 functions to inhibit dendritic branching and promote the development of dendritic spines and excitatory synapses. Interestingly, binding to the calcium-binding protein calmodulin is required for the Rem2 regulation of dendritic branching. However, this interaction is completely dispensable for synapse development. Overall, our results suggest that Rem2 regulates dendritic branching and synapse development via distinct and overlapping signal transduction pathways.
authors.affiliation: Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Ghiretti
authors.forename: Suzanne
authors.initials: S
authors.lastname: Paradis
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape; D018920:Coculture Techniques; D049229:Dendritic Spines / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: D020559:Monomeric GTP-Binding Proteins; C528471:REM2 protein, human; C484604:Rem2 protein, rat