EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration

@article{Wen2004EB1AA,
  title={EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration},
  author={Ying Wen and Christina H. Eng and Jan Schmoranzer and Noemí Cabrera-Poch and Edward J. Morris and M. Chen and Bradley J. Wallar and Arthur S. Alberts and Gregg G. Gundersen},
  journal={Nature Cell Biology},
  year={2004},
  volume={6},
  pages={820-830}
}
Lysophosphatidic acid (LPA) stimulates Rho GTPase and its effector, the formin mDia, to capture and stabilize microtubules in fibroblasts. We investigated whether mammalian EB1 and adenomatous polyposis coli (APC) function downstream of Rho–mDia in microtubule stabilization. A carboxy-terminal APC-binding fragment of EB1 (EB1-C) functioned as a dominant-negative inhibitor of microtubule stabilization induced by LPA or active mDia. Knockdown of EB1 with small interfering RNAs also prevented… 

EB1 Directly Regulates APC-Mediated Actin Nucleation

Microtubule assembly by the Apc protein is regulated by importin-β—RanGTP

Mutations in the tumour suppressor Adenomatous polyposis coli (Apc) initiate most sporadic colorectal cancers. Apc is implicated in regulating microtubule (MT) dynamics in interphase and mitosis.

Amer2 Protein Interacts with EB1 Protein and Adenomatous Polyposis Coli (APC) and Controls Microtubule Stability and Cell Migration*

It is shown that Amer2 (APC membrane recruitment 2), a previously identified membrane-associated APC-binding protein, is a direct interaction partner of EB1 and acts as regulator of microtubule stability together with EB1.

Regulated Binding of Adenomatous Polyposis Coli Protein to Actin*

It is shown that purified carboxyl-terminal basic domain of human APC protein (APC-basic) bound directly to and bundled actin filaments and associated with actin stress fibers in microinjected cells, demonstrating that EB1-APC regulation is direct.

The formin mDia2 stabilizes microtubules independently of its actin nucleation activity

This work generated two actin mutants in a constitutively active version of mDia2 containing formin homology domains 1 and 2 and found that they still induced stable MTs and bound to the MT TIP proteins EB1 and APC, which have also been implicated in MT stabilization.

Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end

A repeat sequence in adenomatous polyposis coli (APC) that binds to EB1's COOH-terminal domain is defined and a similar sequence is identified in members of the microtubule actin cross-linking factor (MACF) family of spectraplakins to provide a structural understanding of how EB1 binds two regulators of microtubules-based cell polarity.

APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment.

Insight is provided into how APC may regulate mitotic spindle function and how errors in chromosome segregation are tolerated in tumor cells.

Structural insights into the EB1–APC interaction

It is found that EB1 is a stable dimer with a parallel coiled coil and show that dimerization is essential for the formation of its C-terminal domain (EB1-C), indicating that the interaction APC–EB1 is posttranslationally regulated in cells.

Nup358 interacts with APC and plays a role in cell polarization

The results indicate that Nup358 cooperates with kinesin-2 to regulate the localization of APC to the cell cortex through a nuclear-transport-independent mechanism, and reveal a more active role for structural nucleoporins in regulating fundamental cellular processes than previously anticipated.
...

References

SHOWING 1-10 OF 57 REFERENCES

Regulation and function of the interaction between the APC tumour suppressor protein and EB1

The interaction between APC and EB1 targets APC to microtubule tips, and that the interaction between the two proteins is down-regulated during mitosis by the previously described mitotic phosphorylation of APC.

The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules

Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome.

It is proposed that a functional interaction between EB1 and p150(Glued) is required for microtubule minus end anchoring at centrosomes during the assembly and maintenance of a radial microtubules array.

Yeast Bim1p Promotes the G1-specific Dynamics of Microtubules

It is reported that a yeast protein of the highly conserved EB1 family, Bim1p, promotes cytoplasmic microtubule dynamics specifically during G1, where microtubules in cells lacking BIM1 showed reduced dynamicity due to a slower shrinking rate, fewer rescues and catastrophes, and more time spent in an attenuated/paused state.

Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle

These results reveal crucial roles for EB1 in mitosis, which is postulate involves its ability to promote the growth and interactions of microtubules within the central spindle and at the cell cortex.

mDia mediates Rho-regulated formation and orientation of stable microtubules

The 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.

Shortstop Recruits EB1/APC1 and Promotes Microtubule Assembly at the Muscle-Tendon Junction

...