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

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Dec 6

PMID 14657163

Citations 26

Authors

Yukio Ishikawa

Hironori Katoh

Manabu Negishi

Affiliations

Soon will be listed here.

Abstract

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.

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References

Loirand G, Cario-Toumaniantz C, Chardin P, Pacaud P . The Rho-related protein Rnd1 inhibits Ca2+ sensitization of rat smooth muscle. J Physiol. 1999; 516 ( Pt 3):825-34. PMC: 2269299. DOI: 10.1111/j.1469-7793.1999.0825u.x. View

Polleux F, Morrow T, Ghosh A . Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature. 2000; 404(6778):567-73. DOI: 10.1038/35007001. View

Tanabe K, Tachibana T, Yamashita T, Che Y, Yoneda Y, Ochi T . The small GTP-binding protein TC10 promotes nerve elongation in neuronal cells, and its expression is induced during nerve regeneration in rats. J Neurosci. 2000; 20(11):4138-44. PMC: 6772628. View

Nakayama A, Harms M, Luo L . Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci. 2000; 20(14):5329-38. PMC: 6772334. View

Katoh H, Yasui H, Yamaguchi Y, Aoki J, Fujita H, Mori K . Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells. Mol Cell Biol. 2000; 20(19):7378-87. PMC: 86291. DOI: 10.1128/MCB.20.19.7378-7387.2000. View

Tashiro A, Minden A, Yuste R . Regulation of dendritic spine morphology by the rho family of small GTPases: antagonistic roles of Rac and Rho. Cereb Cortex. 2000; 10(10):927-38. DOI: 10.1093/cercor/10.10.927. View

Ramakers G . Rho proteins and the cellular mechanisms of mental retardation. Am J Med Genet. 2000; 94(5):367-71. DOI: 10.1002/1096-8628(20001023)94:5<367::aid-ajmg4>3.0.co;2-i. View

Aoki J, Katoh H, Mori K, Negishi M . Rnd1, a novel rho family GTPase, induces the formation of neuritic processes in PC12 cells. Biochem Biophys Res Commun. 2000; 278(3):604-8. DOI: 10.1006/bbrc.2000.3842. View

Penzes P, Johnson R, Sattler R, Zhang X, Huganir R, Kambampati V . The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron. 2001; 29(1):229-42. DOI: 10.1016/s0896-6273(01)00193-3. View

10.

Yamaguchi Y, Katoh H, Yasui H, Mori K, Negishi M . RhoA inhibits the nerve growth factor-induced Rac1 activation through Rho-associated kinase-dependent pathway. J Biol Chem. 2001; 276(22):18977-83. DOI: 10.1074/jbc.M100254200. View

11.

Zhang W, Benson D . Stages of synapse development defined by dependence on F-actin. J Neurosci. 2001; 21(14):5169-81. PMC: 6762826. View

12.

Dunah A, Standaert D . Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane. J Neurosci. 2001; 21(15):5546-58. PMC: 6762635. View

13.

Hering H, Sheng M . Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci. 2001; 2(12):880-8. DOI: 10.1038/35104061. View

14.

Zanata S, Hovatta I, Rohm B, Puschel A . Antagonistic effects of Rnd1 and RhoD GTPases regulate receptor activity in Semaphorin 3A-induced cytoskeletal collapse. J Neurosci. 2002; 22(2):471-7. PMC: 6758682. View

15.

Katoh H, Harada A, Mori K, Negishi M . Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers. Mol Cell Biol. 2002; 22(9):2952-64. PMC: 133765. DOI: 10.1128/MCB.22.9.2952-2964.2002. View

16.

Negishi M, Katoh H . Rho family GTPases as key regulators for neuronal network formation. J Biochem. 2002; 132(2):157-66. DOI: 10.1093/oxfordjournals.jbchem.a003205. View

17.

Fujita H, Katoh H, Ishikawa Y, Mori K, Negishi M . Rapostlin is a novel effector of Rnd2 GTPase inducing neurite branching. J Biol Chem. 2002; 277(47):45428-34. DOI: 10.1074/jbc.M208090200. View

18.

Irie F, Yamaguchi Y . EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP. Nat Neurosci. 2002; 5(11):1117-8. DOI: 10.1038/nn964. View

19.

Ishikawa Y, Katoh H, Nakamura K, Mori K, Negishi M . Developmental changes in expression of small GTPase RhoG mRNA in the rat brain. Brain Res Mol Brain Res. 2002; 106(1-2):145-50. DOI: 10.1016/s0169-328x(02)00413-8. View

20.

Etienne-Manneville S, Hall A . Rho GTPases in cell biology. Nature. 2002; 420(6916):629-35. DOI: 10.1038/nature01148. View