Rac3-induced neuritogenesis requires binding to Neurabin I.
Rac3, a neuronal GTP-binding protein of the Rho family, induces neuritogenesis in primary neurons. Using yeast two-hybrid analysis, we show that Neurabin I, the neuronal F-actin binding protein, is a direct Rac3-interacting molecule. Biochemical and light microscopy studies indicate that Neurabin I copartitions and colocalizes with Rac3 at the growth cones of neurites, inducing Neurabin I association to the cytoskeleton. Moreover, Neurabin I antisense oligonucleotides abolish Rac3-induced neuritogenesis, which in turn is rescued by exogenous Neurabin I but not by Neurabin I mutant lacking the Rac3-binding domain. These results show that Neurabin I mediates Rac3-induced neuritogenesis, possibly by anchoring Rac3 to growth cone F-actin.
Orioli
Donata
D
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, I-27100 Pavia, Italy. orioli@igm.cnr.it
Colaluca
Ivan N
IN
Stefanini
Miria
M
Riva
Silvano
S
Dotti
Carlos G
CG
Peverali
Fiorenzo A
FA
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D020439:Growth Cones / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D047468:Immunoprecipitation; D051379:Mice; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D056921:Nuclear Receptor Coactivator 3; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D051381:Rats; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000099273:Neurabins
D000199:Actins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D056921:Nuclear Receptor Coactivator 3; D020319:Oligodeoxyribonucleotides, Antisense; D014157:Transcription Factors; D000099273:Neurabins