Small GTPases Rac and Rho in the Maintenance of Dendritic Spines and Branches in Hippocampal Pyramidal Neurons

By Ann Y. Nakayama, M. Harms, L. Luo. Journal of Neuroscience, 2000

728 citations recorded by the source corpus.

The shape of dendritic trees and the density of dendritic spines can undergo significant changes during the life of a neuron. We report here the function of the small GTPases Rac and Rho in the maintenance of dendritic structures. Maturing pyramidal neurons in rat hippocampal slice culture were biolistically transfected with dominant GTPase mutants. We found that expression of dominant-negative Rac1 results in a progressive elimination of dendritic spines, whereas hyperactivation of RhoA causes a drastic simplification of dendritic branch patterns that is dependent on the activity of a downstream kinase ROCK. Our results suggest that Rac and Rho play distinct functions in regulating dendritic spines and branches and are vital for the maintenance and reorganization of dendritic structures in maturing neurons.

Subfields: Cell Biology, Cellular and Molecular Neuroscience

View Paper: https://www.semanticscholar.org/paper/891729e819240e4b6a5c0ecfc1e7af6861f8f2eb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. A. Hall
2. Joseph E LeDoux
3. R. Lamprecht
4. Kozo Kaibuchi
5. L. Van Aelst
6. E. Govek
7. S. Newey
8. Masanori Nakayama

In Cellular and Molecular Neuroscience

1. Joseph E LeDoux
2. L. Reichardt
3. Liqun Luo
4. R. Lamprecht
5. A. Hall
6. M. Sheng
7. H. Hering
8. D. O'Leary

Citations in the corpus

• Rho-Kinase/ROCK: A Key Regulator of the Cytoskeleton and Cell Polarity (2010, background): “In Y-27632treated HL-60 cells, the level of activated Rac is increased after stimulation with fMLP, suggesting that the multiple pseudopods observed after the inhibition of Rho/Rho-kinase are the consequence of aberrant activation of Rac.”
• Axon retraction and degeneration in development and disease. (2005, background): “…kinase, Rho kinase (Rok or ROCK), is most critical in RhoA-mediated axon and dendrite retraction because inhibiting this kinase activity completely reverted RhoA-mediated retraction in a number of cases tested in vitro, for example, in cultured hippocampal pyramidal neurons (Nakayama et al. 2000).”
• Structural plasticity and memory (2004, background): “Expression of dominant-negative Rac in young rat hippocampal slices reduces the number of spines on the pyramidal dendrites, and constitutively activated RhoA leads to a simplification of the dendritic tre”
• Neurotrophins: roles in neuronal development and function. (2001, background): “Aberrant expression of constitutively active and dominant negative mutants of these proteins have been shown to have dramatic effects on dendritic branch patterns and spine density (e.g. Li et al 2000, Nakayama et al 2000).”
• Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. (2002, background): “Kalirin is a Trio-like GEF that exists in various splice forms; one of these, Kalirin-7 (the rat homolog of human Duo), which contains only one DH domain specific for Rac, is enriched in the postsynaptic densities (PSD) specifically in dendritic spines.”
• β-catenin is critical for dendritic morphogenesis (2003, neutral): “During dendritic development, the regulation of actin dynamics by the small Rho GTPases is importan”
• The role of the Rho GTPases in neuronal development. (2005, background): “In this study, however, Y-27632 alone did not affect spine density (Nakayama et al. 2000), nor did it affect the spine length of CA1 pyramidal neurons cotransfected with a GFP expression plasmid and a nonspecific siRNA in rat hippocampal slices (Govek et al.”
• Control of Dendritic Arborization by the Phosphoinositide-3′-Kinase–Akt–Mammalian Target of Rapamycin Pathway (2005, neutral): “, 1997); Myc-tagged Rac1 (Nakayama et al., 2000); HA-tagged Arf6T27N (Bose et al.”
• Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. (2003, background): “…efficacy by blocking AMPAR en- formation and maintenance of the spine structure while docytosis. the Rho pathway promotes spine retraction and pre- Third, the actin filaments in the dendritic spines may vents spine formation (Nakayama et al., 2000; Tashiro also support local protein trafficking.”
• RHO GTPASES in neuronal morphogenesis (2000, background): “However, technological advances in imaging and genetic manipulation have allowed the routine examination of the function of candidate genes in dendrite development in physiological setting”
• Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. (2002, background): “This notion has been suggested by previous studies (e.g., in dendrites of hippocampal pyramidal neurons; Nakayama et al. 2000) and was recently demonstrated definitively in the context ofDrosophilamushroom-body neurons.”
• Dentritic spines : structure, dynamics and regulation (2001, background): “cgi?l=5879">Rac1 disrupted the normal spine morphology of pyramidal neurons in slice culture, causing a net increase in dendritic protrusions (filopodia-like processes and LAMELLIPODIA -like ruffles”