spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Summary Freely available
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wittmann, T.
Right arrow Articles by Waterman-Storer, C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wittmann, T.
Right arrow Articles by Waterman-Storer, C. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Cell motility: can Rho GTPases and microtubules point the way?

Torsten Wittmann and Clare M. Waterman-Storer*

The Scripps Research Institute, Department of Cell Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA



View larger version (77K):

[in a new window]
  		Fig. 1. Microtubule cytoskeleton in a migrating Swiss 3T3 fibroblast visualized by the microinjection of X-rhodamine-conjugated tubulin and fluorescence microscopy. The contrast of the images was inverted to show individual microtubules more clearly. Note how microtubules are aligned along the axis of migration and how growing microtubules fill in the protruding leading edge as the cell moves forward.

 


View larger version (23K):

[in a new window]
  		Fig. 2. Polarization of the microtubule cytoskeleton in a migrating cell. (a) In many cell types, the centrosome reorients towards the direction of migration (black arrow). (b) Stable, detyrosinated microtubules (purple) appear to be oriented preferentially in the direction of migration. (c) Microtubules exhibit net growth near the leading edge and, (d) as a result of actin-dependent retrograde flow (orange arrow) buckle and break in the cell body, creating depolymerising microtubule minus ends and dynamic plus ends. (e) Microtubule plus-end-binding proteins such as APC or CLASPs might stabilize growing microtubule ends in the leading edge. In this and all subsequent figures, the open arrow indicates the direction of cell migration. Thick black lines represent microtubules. Green and red arrows indicate growing or shrinking microtubules, respectively, and plus and minus signs indicate microtubule polarity.

 


View larger version (24K):

[in a new window]
  		Fig. 3. Potential mechanisms for how asymmetries of the microtubule cytoskeleton might establish cell polarization. (a) Targeting of focal adhesions in the rear of the cell and kinesin-dependent transport of a focal-adhesion-dissociation factor to the adhesion sites might induce the retraction of the cell tail. (b-f) Microtubules might modulate the activity of Rho GTPases by a number of hypothetical mechanisms: (b) the activity of GEFs could be regulated simply by their association with the microtubule cytoskeleton; (c) in the case of RhoA, GEFs such as p190RhoGEF could be activated by their release from depolymerising microtubules in the cell body; (d) the local activation of a RhoG-specific GEF, TrioGEF1, and thus RhoG, a Rho protein upstream of Rac1 and Cdc42Hs, appears to be dependent on some sort of kinesin-mediated transport process; (e) association with the microtubule-plus-end-binding protein APC that is enriched in the lamellipodium could locally activate Rac1-specific GEFs such as Asef; (f) finally, microtubule-dependent regulation of phosphoinositide 3-kinase could activate Rac1 through PtdIns(3,4,5)P3-binding GEFs such as Vav.

 


View larger version (25K):

[in a new window]
  		Fig. 4. Potential mechanisms for how Rho proteins could regulate aspects of the microtubule cytoskeleton. (a) Stable, detyrosinated microtubules (purple) are induced by RhoA. (b) RhoA might also cause the phosphorylation of microtubule-associated proteins and thus destabilize microtubules. (c) Rac1 and Cdc42Hs might decrease the microtubule catastrophe frequency and thus promote microtubule growth through Pak1-dependent phosphorylation of stathmin/Op18. (d) Cdc42Hs activity is required for the reorientation of the centrosome towards the direction of migration, which could occur through cortical cytoplasmic dynein activity.

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



© The Company of Biologists Ltd 2001