Anti-ganglioside antibody-mediated activation of RhoA induces inhibition of neurite outgrowth

Gang Zhang, Helmar C. Lehmann, Sowmia Manoharan, Mohammedali Hashmi, Sangwoo Shim, Guo Li Ming, Ronald L. Schnaar, Pablo H. Lopez, Nataliia Bogdanova, Kazim A. Sheikh

Research output: Contribution to journalArticlepeer-review

Abstract

Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barré syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al., 2007). An implication of these findings is that anti-GD1a Abs can mediate inhibition of axon regeneration and limit recovery in some patients with GBS. The downstream inhibitory intracellular signaling that mediates anti-ganglioside Ab-induced axon inhibition remains unclear. In the current study, we show that disease-relevant and GBS patient's anti-ganglioside Abs can inhibit neurite outgrowth in dissociated primary neuronal cultures. Activation of small GTPase RhoA and its key downstream effector Rho kinase (ROCK) are critical mediators of growth cone and neurite outgrowth inhibition. Therefore, we examined the role of these intracellular signaling molecules in our primary neuronal cultures by molecular and pharmacologic approaches. Our results show that the Ab-mediated inhibition of neurite outgrowth involves the activation of RhoA and ROCK pathway and this activation is through the engagement of specific cell-surface gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway involved in anti-ganglioside Ab-mediated inhibition of neurite outgrowth.

Original languageEnglish (US)
Pages (from-to)1664-1675
Number of pages12
JournalJournal of Neuroscience
Volume31
Issue number5
DOIs
StatePublished - Feb 2 2011
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Anti-ganglioside antibody-mediated activation of RhoA induces inhibition of neurite outgrowth'. Together they form a unique fingerprint.

Cite this