Drosophila RhoGEF4 encodes a novel RhoA-specific guanine exchange factor that is highly expressed in the embryonic central nervous system.
Rho family small GTPases act as molecular switches that regulate neuronal morphogenesis, including axon growth and guidance, dendritic spine formation, and synapse formation. These proteins are positively regulated by guanine nucleotide exchange factors (GEFs) of the Dbl family. This study describes the identification and characterization of Drosophila RhoGEF4 (DRhoGEF4), a novel Dbl family protein that is specifically expressed in the central nervous system during Drosophila embryogenesis. The predicted amino acid sequence of DRhoGEF4 contains a Dbl homology (DH) domain and an adjacent C-terminal pleckstrin homology (PH) domain, which are most closely related to those of mammalian frabins. In this study, the DH-PH motif is shown to enhance the dissociation of GDP from either RhoA or Rac1 but not from Cdc42 in vitro. In addition, p21-binding domain pull-down assays demonstrate that DRhoGEF4 activates RhoA, but neither Rac1 nor Cdc42 in HEK293 cells. Finally, overexpression of DRhoGEF4 is able to induce assembly of stress fibers in cultured NIH3T3 cells. Taken together, these findings suggest that DRhoGEF4 may participate in cytoskeleton-related cellular events by specifically activating RhoA in neuronal morphogenesis.
Nahm
Minyeop
M
Interdisciplinary Program in Brain Science, School of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Lee
Mihye
M
Baek
Seung-Hak
SH
Yoon
Jin-Ho
JH
Kim
Hong-Hee
HH
Lee
Zang Hee
ZH
Lee
Seungbok
S
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000196:embryology; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; C516327:RhoGEF4 protein, Drosophila; D020742:rhoA GTP-Binding Protein