A Role of Rnd1 GTPase in Dendritic Spine Formation in Hippocampal Neurons

Rho family of small GTPases are key regulators for morphological changes of neurons on the basis of reorganization of the actin cytoskeleton. Rnd1, a novel member of this family, is predominantly expressed in neurons in brain; however, the neuronal functions of Rnd1 are not known. Here we investigated the effect of Rnd1 on neuronal morphology. Northern blot analysis of Rnd1 expression in rat brain showed that Rnd1 mRNA was highly expressed during early postnatal period, the synaptogenic stage. In situ hybridization analysis at this period revealed that Rnd1 mRNA was strongly expressed in neurons, including the hippocampal pyramidal neurons. Furthermore, immunoblot analysis showed that Rnd1 protein was localized in synaptosomal membrane fraction. Ectopical overexpression of Rnd1 in cultured rat hippocampal neurons promoted the elongation of dendritic spines. On the other hand, suppression of endogenous Rnd1 level by antisense oligonucleotide of Rnd1 caused the increase in the percentage of headless protrusions accompanied by the reduction in the spine number and spine width and shortened the length of the headless protrusions. These results indicate that Rnd1 plays a role in spine formation in the developmental synaptogenic stage.

[1]  Liqun Luo,et al.  Small GTPase Cdc42 Is Required for Multiple Aspects of Dendritic Morphogenesis , 2003, The Journal of Neuroscience.

[2]  R. Huganir,et al.  Rapid Induction of Dendritic Spine Morphogenesis by trans-Synaptic EphrinB-EphB Receptor Activation of the Rho-GEF Kalirin , 2003, Neuron.

[3]  A. Hall,et al.  Rho GTPases in cell biology , 2002, Nature.

[4]  K. Mori,et al.  Rapostlin Is a Novel Effector of Rnd2 GTPase Inducing Neurite Branching* , 2002, The Journal of Biological Chemistry.

[5]  Y. Yamaguchi,et al.  EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP , 2002, Nature Neuroscience.

[6]  K. Mori,et al.  Developmental changes in expression of small GTPase RhoG mRNA in the rat brain. , 2002, Brain research. Molecular brain research.

[7]  H. Katoh,et al.  Rho family GTPases as key regulators for neuronal network formation. , 2002, Journal of biochemistry.

[8]  K. Mori,et al.  Socius Is a Novel Rnd GTPase-Interacting Protein Involved in Disassembly of Actin Stress Fibers , 2002, Molecular and Cellular Biology.

[9]  S. Zanata,et al.  Antagonistic Effects of Rnd1 and RhoD GTPases Regulate Receptor Activity in Semaphorin 3A-Induced Cytoskeletal Collapse , 2002, The Journal of Neuroscience.

[10]  M. Sheng,et al.  Dentritic spines : structure, dynamics and regulation , 2001, Nature Reviews Neuroscience.

[11]  D. Standaert,et al.  Dopamine D1 Receptor-Dependent Trafficking of Striatal NMDA Glutamate Receptors to the Postsynaptic Membrane , 2001, The Journal of Neuroscience.

[12]  D. Benson,et al.  Stages of Synapse Development Defined by Dependence on F-Actin , 2001, The Journal of Neuroscience.

[13]  M Negishi,et al.  RhoA Inhibits the Nerve Growth Factor-induced Rac1 Activation through Rho-associated Kinase-dependent Pathway* , 2001, The Journal of Biological Chemistry.

[14]  R. Huganir,et al.  The Neuronal Rho-GEF Kalirin-7 Interacts with PDZ Domain–Containing Proteins and Regulates Dendritic Morphogenesis , 2001, Neuron.

[15]  H. Katoh,et al.  Rnd1, a novel rho family GTPase, induces the formation of neuritic processes in PC12 cells. , 2000, Biochemical and biophysical research communications.

[16]  G. Ramakers Rho proteins and the cellular mechanisms of mental retardation. , 2000, American journal of medical genetics.

[17]  Y. Yamaguchi,et al.  Small GTPase RhoG Is a Key Regulator for Neurite Outgrowth in PC12 Cells , 2000, Molecular and Cellular Biology.

[18]  R. Yuste,et al.  Regulation of dendritic spine morphology by the rho family of small GTPases: antagonistic roles of Rac and Rho. , 2000, Cerebral cortex.

[19]  Ann Y. Nakayama,et al.  Small GTPases Rac and Rho in the Maintenance of Dendritic Spines and Branches in Hippocampal Pyramidal Neurons , 2000, The Journal of Neuroscience.

[20]  H. Yoshikawa,et al.  The Small GTP-Binding Protein TC10 Promotes Nerve Elongation in Neuronal Cells, and Its Expression Is induced during Nerve Regeneration in Rats , 2000, The Journal of Neuroscience.

[21]  Anirvan Ghosh,et al.  Semaphorin 3A is a chemoattractant for cortical apical dendrites , 2000, Nature.

[22]  P. Pacaud,et al.  The Rho‐related protein Rnd1 inhibits Ca2+ sensitization of rat smooth muscle , 1999, The Journal of physiology.

[23]  P. Scambler,et al.  RhoE Regulates Actin Cytoskeleton Organization and Cell Migration , 1998, Molecular and Cellular Biology.

[24]  M. Mattei,et al.  A New Member of the Rho Family, Rnd1, Promotes Disassembly of Actin Filament Structures and Loss of Cell Adhesion , 1998, The Journal of cell biology.

[25]  A. Hall,et al.  Rho GTPases and the actin cytoskeleton. , 1998, Science.

[26]  Richard Threadgill,et al.  Regulation of Dendritic Growth and Remodeling by Rho, Rac, and Cdc42 , 1997, Neuron.

[27]  Stephen J. Smith,et al.  Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation , 1996, Neuron.

[28]  J. Settleman,et al.  Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation , 1996, Molecular and cellular biology.

[29]  Y. Jan,et al.  Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines , 1996, Nature.

[30]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[31]  Anne J. Ridley,et al.  The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors , 1992, Cell.

[32]  G. Banker,et al.  Culturing nerve cells , 1998 .