title: RIM3γ and RIM4γ are key regulators of neuronal arborization.
abstract: The large isoforms of the Rab3 interacting molecule (RIM) family, RIM1α/β and RIM2α/β, have been shown to be centrally involved in mediating presynaptic active zone function. The RIM protein family contains two additional small isoforms, RIM3γ and RIM4γ, which are composed only of the RIM-specific C-terminal C2B domain and varying N-terminal sequences and whose function remains to be elucidated. Here, we report that both, RIM3γ and RIM4γ, play an essential role for the development of neuronal arborization and of dendritic spines independent of synaptic function. γ-RIM knock-down in rat primary neuronal cultures and in vivo resulted in a drastic reduction in the complexity of neuronal arborization, affecting both axonal and dendritic outgrowth, independent of the time point of γ-RIM downregulation during dendrite development. Rescue experiments revealed that the phenotype is caused by a function common to both γ-RIMs. These findings indicate that γ-RIMs are involved in cell biological functions distinct from the regulation of synaptic vesicle exocytosis and play a role in the molecular mechanisms controlling the establishment of dendritic complexity and axonal outgrowth.
authors.affiliation: Department of Neuropathology, Department of Epileptology, Laboratory for Experimental Epileptology and Cognition Research, University of Bonn, 53105 Bonn, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Alvarez-Baron
authors.forename: Katrin
authors.initials: K
authors.lastname: Michel
authors.forename: Tobias
authors.initials: T
authors.lastname: Mittelstaedt
authors.forename: Thoralf
authors.initials: T
authors.lastname: Opitz
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Dirk
authors.initials: D
authors.lastname: Dietrich
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D003712:Dendrites / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005260:Female; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics; D006056:Golgi Apparatus / Q000502:physiology / Q000648:ultrastructure; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016086:Lentivirus / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D014162:Transfection
chemical_list: D017931:DNA Primers; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C411651:Rims3 protein, rat