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


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online July 23, 2008
doi: 10.1242/10.1242/jcs.018044

Journal of Cell Science 121, 2435-2444 (2008)
Published by The Company of Biologists 2008
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 Deakin, N. O.
Right arrow Articles by Turner, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Deakin, N. O.
Right arrow Articles by Turner, C. E.
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?

Paxillin comes of age

Nicholas O. Deakin and Christopher E. Turner*

Department of Cell and Developmental Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA


Figure 1
View larger version (28K):
[in this window]
[in a new window]

  		Fig. 1. Focal adhesions provide both a structural and a signaling link between the ECM and the actin cytoskeleton. The adhesion of a cell to the ECM, via transmembrane {alpha}β-integrin heterodimers, leads to integrin activation and the recruitment of numerous intracellular proteins to the plasma membrane. Focal adhesions are now known to comprise over 125 protein species (only selected examples are depicted), which include both structural proteins (which mediate a physical link to the actin cytoskeleton) and regulatory proteins (which have a major role in the modulation of actin dynamics for productive cell migration). Proteins such as paxillin serve as scaffold proteins to facilitate the functional integration of these different categories of focal-adhesion proteins.

 

Figure 2
View larger version (56K):
[in this window]
[in a new window]

  		Fig. 2. The LD4 motif of paxillin regulates cell protrusion and retraction. CHO-K1 cells stably transfected with (A) wild-type paxillin or (B) a mutant of paxillin that lacks the LD4 motif ({Delta}LD4) were spread on 10 µg/ml fibronectin for 2 hours in the presence of serum. Cells were fixed and stained for F-actin (red) and paxillin (green). Deletion of the LD4 domain of paxillin results in extensive peripheral protrusive activity (arrows) and defective tail retraction (arrowhead). It is also of note that the protrusions observed in cells that express paxillin{Delta}LD4 contain numerous dot-like paxillin-rich focal complexes at their periphery, which are less prevalent in cells that express wild-type paxillin. Scale bars: 20 µm.

 

Figure 3
View larger version (27K):
[in this window]
[in a new window]

  		Fig. 3. The coordination of Rac1 signaling by the paxillin LD4 motif. Paxillin is one of the earliest proteins that is recruited to nascent focal adhesions and is necessary for the turnover of focal adhesions during cell migration. The engagement of integrins with the extracellular matrix results in the localized activation of Rac1 and the Src and FAK tyrosine kinases. Together, Rac1, Src and FAK promote the recruitment of the GIT-PIX-PAK-NCK complex to focal adhesions by means of an interaction between the paxillin-binding subdomain 2 (PBS2) of GIT and the paxillin LD4 motif. Rac1 mediates this process by binding to and activating its effector PAK, which stimulates a multi-step conformational remodeling of the GIT-PIX-PAK-NCK complex and the PAK-dependent phosphorylation of the paxillin LD4 motif at S273. Src-FAK-dependent phosphorylation of GIT is also necessary for GIT binding to paxillin. The Rac1 GEF activity of PIX might function in a feed-forward loop to further promote localized Rac1 signaling to PAK at the leading edge of the cell. The recruitment of the GIT-PIX-PAK-NCK complex to paxillin also serves as a termination signal for Rac1 activity. This is also regulated at multiple levels, including the PTP-PEST-dependent tyrosine dephosphorylation of GIT, paxillin and FAK, as well as the GIT-dependent inhibition of Arf6 signaling to Rac1 (not shown). The serine/threonine phosphatase PP2A might also be recruited to paxillin to dephosphorylate S273. PS, phosphorylated serine; PY, phosphorylated tyrosine.

 

Figure 4
View larger version (89K):
[in this window]
[in a new window]

  		Fig. 4. Paxillin is enriched in adhesions of fibroblasts migrating on either 2D or 3D fibronectin matrices. Mouse embryonic fibroblasts (MEFs) were allowed to migrate for 16 hours in the presence of serum on (A) a 2D fibronectin-coated surface or (B) a 3D cell-derived fibronectin-rich matrix (CDM) that is more representative of the in vivo environment. Cells were fixed and stained for F-actin (red), paxillin (green) and fibronectin (blue). Although paxillin-rich adhesions are observed in both conditions, MEFs migrating on the 2D fibronectin are well-spread and exhibit robust actin stress fibers, whereas cells migrating within the 3D CDM display long, thin protrusions (arrows) and limited actin organization. Scale bar: 20 µm.

 

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 2008