The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

Overview

Journal J Neurosci

Specialty Neurology

Date 2007 Apr 27

PMID 17460085

Citations 41

Authors

Pamela J Lein

Xin Guo

Geng-Xian Shi

Melissa Moholt-Siebert

Donald Bruun

Douglas A Andres

Affiliations

Soon will be listed here.

Abstract

The Rit GTPase is widely expressed in developing and adult nervous systems, and our previous data with pheochromocytoma cells implicate Rit signaling in NGF-induced neurite outgrowth. In this study, we investigated a role for Rit in neuronal morphogenesis. Expression of a dominant-negative (dn) Rit mutant in hippocampal neurons inhibited axonal growth but potentiated dendritic growth. Conversely, a constitutively active (ca) Rit mutant promoted axonal growth but inhibited dendritic growth. Dendritogenesis is regulated differently in sympathetic neurons versus hippocampal neurons in that sympathetic neurons require NGF and bone morphogenetic proteins (BMPs) to trigger dendritic growth. Despite these differences, dnRit potentiated and caRit blocked BMP7-induced dendritic growth in sympathetic neurons. Biochemical studies indicated that BMP7 treatments that caused dendritic growth also decreased Rit GTP loading. Additional studies demonstrate that caRit increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and pharmacological inhibition of MEK1 (mitogen-activated protein kinase/ERK 1) blocked the axon-promoting and dendrite-inhibiting effects of caRit. These observations suggest that Rit is a convergence point for multiple signaling pathways and it functions to promote axonal growth but inhibit dendritic growth via activation of ERK1/2. Modulation of the activational status of Rit may therefore represent a generalized mechanism across divergent neuronal cell types for regulating axonal versus dendritic growth modes.

Citing Articles

RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities.

Wu L, Wang F, Moncman C, Pandey M, Clarke H, Frazier H Heliyon. 2023; 9(10):e20384.

PMID: 37780758 PMC: 10539968. DOI: 10.1016/j.heliyon.2023.e20384.

Gamma secretase activity modulates BMP-7-induced dendritic growth in primary rat sympathetic neurons.

Karunungan K, Garza R, Grodzki A, Holt M, Lein P, Chandrasekaran V Auton Neurosci. 2023; 247:103085.

PMID: 37031474 PMC: 10330319. DOI: 10.1016/j.autneu.2023.103085.

LZTR1: A promising adaptor of the CUL3 family.

Zhang H, Cao X, Wang J, Li Q, Zhao Y, Jin X Oncol Lett. 2021; 22(1):564.

PMID: 34113392 PMC: 8185703. DOI: 10.3892/ol.2021.12825.

The molecular functions of RIT1 and its contribution to human disease.

Van R, Cuevas-Navarro A, Castel P, McCormick F Biochem J. 2020; 477(15):2755-2770.

PMID: 32766847 PMC: 7787054. DOI: 10.1042/BCJ20200442.

The Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases.

Qu L, Pan C, He S, Lang B, Gao G, Wang X Front Mol Neurosci. 2019; 12:121.

PMID: 31213978 PMC: 6555388. DOI: 10.3389/fnmol.2019.00121.

References

Arimura N, Kaibuchi K . Key regulators in neuronal polarity. Neuron. 2005; 48(6):881-4. DOI: 10.1016/j.neuron.2005.11.007. View

Yoshimura T, Arimura N, Kawano Y, Kawabata S, Wang S, Kaibuchi K . Ras regulates neuronal polarity via the PI3-kinase/Akt/GSK-3beta/CRMP-2 pathway. Biochem Biophys Res Commun. 2005; 340(1):62-8. DOI: 10.1016/j.bbrc.2005.11.147. View

Massague J, Gomis R . The logic of TGFbeta signaling. FEBS Lett. 2006; 580(12):2811-20. DOI: 10.1016/j.febslet.2006.04.033. View

Scott E, Luo L . How do dendrites take their shape?. Nat Neurosci. 2001; 4(4):359-65. DOI: 10.1038/86006. View

Bateman J, Van Vactor D . The Trio family of guanine-nucleotide-exchange factors: regulators of axon guidance. J Cell Sci. 2001; 114(Pt 11):1973-80. DOI: 10.1242/jcs.114.11.1973. View

Estrach S, Schmidt S, Diriong S, Penna A, Blangy A, Fort P . The Human Rho-GEF trio and its target GTPase RhoG are involved in the NGF pathway, leading to neurite outgrowth. Curr Biol. 2002; 12(4):307-12. DOI: 10.1016/s0960-9822(02)00658-9. View

Spencer M, Shao H, Tucker H, Andres D . Nerve growth factor-dependent activation of the small GTPase Rin. J Biol Chem. 2002; 277(20):17605-15. DOI: 10.1074/jbc.M111400200. View

Kim I, Beck H, Lein P, Higgins D . Interferon gamma induces retrograde dendritic retraction and inhibits synapse formation. J Neurosci. 2002; 22(11):4530-9. PMC: 6758811. DOI: 20026431. View

Spencer M, Shao H, Andres D . Induction of neurite extension and survival in pheochromocytoma cells by the Rit GTPase. J Biol Chem. 2002; 277(23):20160-8. DOI: 10.1074/jbc.M201092200. View

10.

Goldberg J, Klassen M, Hua Y, Barres B . Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science. 2002; 296(5574):1860-4. DOI: 10.1126/science.1068428. View

11.

Vaillant A, Zanassi P, Walsh G, Aumont A, Alonso A, Miller F . Signaling mechanisms underlying reversible, activity-dependent dendrite formation. Neuron. 2002; 34(6):985-98. DOI: 10.1016/s0896-6273(02)00717-1. View

12.

Redmond L, Kashani A, Ghosh A . Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron. 2002; 34(6):999-1010. DOI: 10.1016/s0896-6273(02)00737-7. View

13.

May V, Schiller M, Eipper B, Mains R . Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms. J Neurosci. 2002; 22(16):6980-90. PMC: 6757900. DOI: 20026718. View

14.

Lonze B, Ginty D . Function and regulation of CREB family transcription factors in the nervous system. Neuron. 2002; 35(4):605-23. DOI: 10.1016/s0896-6273(02)00828-0. View

15.

Lein P, Beck H, Chandrasekaran V, Gallagher P, Chen H, Lin Y . Glia induce dendritic growth in cultured sympathetic neurons by modulating the balance between bone morphogenetic proteins (BMPs) and BMP antagonists. J Neurosci. 2002; 22(23):10377-87. PMC: 6758753. View

16.

Shi S, Jan L, Jan Y . Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell. 2003; 112(1):63-75. DOI: 10.1016/s0092-8674(02)01249-7. View

17.

Hynds D, Spencer M, Andres D, Snow D . Rit promotes MEK-independent neurite branching in human neuroblastoma cells. J Cell Sci. 2003; 116(Pt 10):1925-35. DOI: 10.1242/jcs.00401. View

18.

Wayman G, Impey S, Marks D, Saneyoshi T, Grant W, Derkach V . Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006; 50(6):897-909. DOI: 10.1016/j.neuron.2006.05.008. View

19.

Song H, Ming G, He Z, Lehmann M, McKerracher L, Tessier-Lavigne M . Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science. 1998; 281(5382):1515-8. DOI: 10.1126/science.281.5382.1515. View

20.

Vaughan P, Pike C, Cotman C, Cunningham D . Thrombin receptor activation protects neurons and astrocytes from cell death produced by environmental insults. J Neurosci. 1995; 15(7 Pt 2):5389-401. PMC: 6577903. View