Promotion of Axon Regeneration by Myelin-associated Glycoprotein and Nogo Through Divergent Signals Downstream of Gi/G

Overview

Journal J Neurosci

Specialty Neurology

Date 2004 Jul 30

PMID 15282288

Citations 34

Authors

Yuiko Hasegawa

Masashi Fujitani

Katsuhiko Hata

Masaya Tohyama

Satoru Yamagishi

Toshihide Yamashita

Affiliations

Soon will be listed here.

Abstract

Several myelin-derived proteins have been identified as components of the CNS myelin that prevents axonal regeneration in the adult vertebrate CNS. Activation of RhoA has been shown to be an essential part of the signaling mechanism of these proteins. Here we report an additional signal, which determines whether these proteins promote or inhibit axon outgrowth. Myelin-associated glycoprotein (MAG) and Nogo trigger the intracellular elevation of Ca2+ as well as the activation of PKC, presumably mediated by G(i)/G. Neurite outgrowth inhibition and growth cone collapse by MAG or Nogo can be converted to neurite extension and growth cone spreading by inhibiting conventional PKC, but not by inhibiting inositol 1,4,5-triphosphate (IP3). Conversely, neurite growth of immature neurons promoted by MAG is abolished by inhibiting IP3. Activation of RhoA is independent of PKC. Thus, a balance between PKC and IP3 is important for bidirectional regulation of axon regeneration by the myelin-derived proteins.

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References

Cai D, Shen Y, De Bellard M, Tang S, Filbin M . Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron. 1999; 22(1):89-101. DOI: 10.1016/s0896-6273(00)80681-9. View

Miranti C, Ohno S, Brugge J . Protein kinase C regulates integrin-induced activation of the extracellular regulated kinase pathway upstream of Shc. J Biol Chem. 1999; 274(15):10571-81. DOI: 10.1074/jbc.274.15.10571. View

Davies A . Neurotrophins: neurotrophic modulation of neurite growth. Curr Biol. 2000; 10(5):R198-200. DOI: 10.1016/s0960-9822(00)00351-1. View

Fournier A, Grandpre T, Strittmatter S . Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature. 2001; 409(6818):341-6. DOI: 10.1038/35053072. View

Cai D, Qiu J, Cao Z, McAtee M, Bregman B, Filbin M . Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci. 2001; 21(13):4731-9. PMC: 6762375. View

Yamashita T, Higuchi H, Tohyama M . The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J Cell Biol. 2002; 157(4):565-70. PMC: 2173856. DOI: 10.1083/jcb.200202010. View

Neumann S, Bradke F, Tessier-Lavigne M, Basbaum A . Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron. 2002; 34(6):885-93. DOI: 10.1016/s0896-6273(02)00702-x. View

Qiu J, Cai D, Dai H, McAtee M, Hoffman P, Bregman B . Spinal axon regeneration induced by elevation of cyclic AMP. Neuron. 2002; 34(6):895-903. DOI: 10.1016/s0896-6273(02)00730-4. View

Schmidt A, Hall A . Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 2002; 16(13):1587-609. DOI: 10.1101/gad.1003302. View

10.

Xiang Y, Li Y, Zhang Z, Cui K, Wang S, Yuan X . Nerve growth cone guidance mediated by G protein-coupled receptors. Nat Neurosci. 2002; 5(9):843-8. DOI: 10.1038/nn899. View

11.

Cai D, Deng K, Mellado W, Lee J, Ratan R, Filbin M . Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron. 2002; 35(4):711-9. DOI: 10.1016/s0896-6273(02)00826-7. View

12.

Dechant G, Barde Y . The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci. 2002; 5(11):1131-6. DOI: 10.1038/nn1102-1131. View

13.

McKerracher L, Winton M . Nogo on the go. Neuron. 2002; 36(3):345-8. DOI: 10.1016/s0896-6273(02)01018-8. View

14.

Wang K, Kim J, Sivasankaran R, Segal R, He Z . P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature. 2002; 420(6911):74-8. DOI: 10.1038/nature01176. View

15.

Wong S, Henley J, Kanning K, Huang K, Bothwell M, Poo M . A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat Neurosci. 2002; 5(12):1302-8. DOI: 10.1038/nn975. View

16.

Niederost B, Oertle T, Fritsche J, McKinney R, Bandtlow C . Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci. 2002; 22(23):10368-76. PMC: 6758757. View

17.

Yamashita T, Tohyama M . The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci. 2003; 6(5):461-7. DOI: 10.1038/nn1045. View

18.

Sivasankaran R, Pei J, Wang K, Zhang Y, Shields C, Xu X . PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci. 2004; 7(3):261-8. DOI: 10.1038/nn1193. View

19.

Doherty P, Fruns M, Seaton P, Dickson G, Barton C, Sears T . A threshold effect of the major isoforms of NCAM on neurite outgrowth. Nature. 1990; 343(6257):464-6. DOI: 10.1038/343464a0. View

20.

Johnson P, Abramow-Newerly W, Seilheimer B, Sadoul R, Tropak M, Arquint M . Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function. Neuron. 1989; 3(3):377-85. DOI: 10.1016/0896-6273(89)90262-6. View