Identification of Neurochondrin as a new interaction partner of the FH3 domain of the Diaphanous-related formin Dia1.
Mammalian Diaphanous (Dia)-related formins initiate the assembly of filamentous actin downstream of Rho GTPases to regulate cellular processes such as cytokinesis, cell polarity, cell motility and adhesion. In this work, we show that Neurochondrin (NC) is a novel Dia1 interacting protein. NC specifically binds to the formin homology 3 (FH3), but not to the FH1 or FH2 domain of Dia1. Both proteins show a partial co-localization in dissociated primary rat hippocampal neurons. Ectopic expression of both proteins induced neurite outgrowth in Neuro2A cells. Using a series of deletion mutants of NC we could show that the first 100 amino acids were responsible for its effect on neurite outgrowth, whereas the C-terminal part of NC had no neurite outgrowth promoting activity. Moreover, co-expression of the C terminus of NC with Dia1DeltaDAD resulted in a dramatic reduction of Dia1-induced neurite outgrowth. On the basis of actin fractionation assays, SRF-activity assays as well as microtubule stabilization assays, we could demonstrate that the C terminus of NC does not influence the actin polymerizing activity of Dia1, indicating a more specific function of NC in the modulation of Dia1 activity.
Schwaibold
Eva M C
EM
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Brandt
Dominique T
DT
D000818:Animals; D042966:Cytochrome-B(5) Reductase / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D017384:Sequence Deletion
D009419:Nerve Tissue Proteins; C119189:neurochondrin; C528412:Cyb5R3 protein, rat; D042966:Cytochrome-B(5) Reductase