mDia mediates Rho-regulated formation and orientation of stable microtubules.
Rho-GTPase stabilizes microtubules that are oriented towards the leading edge in serum-starved 3T3 fibroblasts through an unknown mechanism. We used a Rho-effector domain screen to identify mDia as a downstream Rho effector involved in microtubule stabilization. Constitutively active mDia or activation of endogenous mDia with the mDia-autoinhibitory domain stimulated the formation of stable microtubules that were capped and oriented towards the wound edge. mDia co-localized with stable microtubules when overexpressed and associated with microtubules in vitro. Rho kinase was not necessary for the formation of stable microtubules. Our results show that mDia is sufficient to generate and orient stable microtubules, and indicate that Dia-related formins are part of a conserved pathway that regulates the dynamics of microtubule ends.
Palazzo
A F
AF
Department of Anatomy & Cell Biology, Columbia University, New York 10032, USA.
Cook
T A
TA
Alberts
A S
AS
Gundersen
G G
GG
D016475:3T3 Cells / Q000166:cytology / Q000201:enzymology*; D000818:Animals; D016764:Cell Polarity / Q000235:genetics*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000493:pharmacokinetics; D051379:Mice; D008870:Microtubules / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D054460:rho-Associated Kinases
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins