GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation

Brad Bryan, Vikas Kumar, Lewis Joe Stafford, Yi Cai, Gangyi Wu, Mingyao Liu

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The Rho family of small GTPases controls a wide range of cellular processes in eukaryotic cells, such as normal cell growth, proliferation, differentiation, gene regulation, actin cytoskeletal organization, cell fate determination, and neurite outgrowth. The activation of Rho-GTPases requires the exchange of GDP for GTP, a process catalyzed by the Dbl family of guanine nucleotide exchange factors. We demonstrate that a newly identified guanine nucleotide exchange factor, GEFT, is widely expressed in the brain and highly concentrated in the hippocampus, and the Purkinje and granular cells of the cerebellum. Exogenous expression of GEFT promotes dendrite outgrowth in hippocampal neurons, resulting in spines with larger size as compared with control spines. In neuroblastoma cells, GEFT promotes the active GTP-bound state of Rac1, Cdc42, and RhoA and increases neurite outgrowth primarily via Rac1. Furthermore, we demonstrated that PAK1 and PAK5, both downstream effectors of Rac1/Cdc42, are necessary for GEFT-induced neurite outgrowth. AP-1 and NF-κB, two transcriptional factors involved in neurite outgrowth and survival, were up-regulated in GEFT-expressing cells. Together, our data suggest that GEFT enhances dendritic spine formation and neurite outgrowth in primary neurons and neuroblastoma cells, respectively, through the activation of Rac/Cdc42-PAK signaling pathways.

Original languageEnglish (US)
Pages (from-to)45824-45832
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number44
DOIs
StatePublished - Oct 29 2004

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Rho Guanine Nucleotide Exchange Factors
Guanine Nucleotide Exchange Factors
Dendritic Spines
Guanosine Triphosphate
Neurons
Chemical activation
rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Transcription Factor AP-1
Cell growth
Gene expression
Actins
Brain
Ion exchange
Neuroblastoma
Spine
Purkinje Cells
Eukaryotic Cells
Dendrites
Cerebellum

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bryan, Brad ; Kumar, Vikas ; Stafford, Lewis Joe ; Cai, Yi ; Wu, Gangyi ; Liu, Mingyao. / GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 44. pp. 45824-45832.
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GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation. / Bryan, Brad; Kumar, Vikas; Stafford, Lewis Joe; Cai, Yi; Wu, Gangyi; Liu, Mingyao.

In: Journal of Biological Chemistry, Vol. 279, No. 44, 29.10.2004, p. 45824-45832.

Research output: Contribution to journalArticle

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