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  Focal adhesion kinase modulates Cdc42 activity downstream of positive and negative axon guidance cues

Myers, J. P., Robles, E., Ducharme-Smith, A., & Gomez, T. M. (2012). Focal adhesion kinase modulates Cdc42 activity downstream of positive and negative axon guidance cues. Journal of Cell Science, 125(12), 2918-2929. doi:10.1242/jcs.100107.

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 Creators:
Myers, Jonathan P., Author
Robles, Estuardo1, Author           
Ducharme-Smith, Allison, Author
Gomez, Timothy M., Author
Affiliations:
1Department: Genes-Circuits-Behavior / Baier, MPI of Neurobiology, Max Planck Society, ou_1128545              

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Free keywords: GROWTH CONE FILOPODIA; SRC FAMILY KINASES; N-WASP ACTIVITY; NEURITE OUTGROWTH; RHOA ACTIVITY; LIVING CELLS; COLLAPSE; COMPLEX; LAMELLIPODIA; ACTIVATIONAxon guidance; Pathfinding; Neural development;
 Abstract: There is biochemical, imaging and functional evidence that Rho GTPase signaling is a crucial regulator of actin-based structures such as lamellipodia and filopodia. However, although Rho GTPases are believed to serve similar functions in growth cones, the spatiotemporal dynamics of Rho GTPase signaling has not been examined in living growth cones in response to known axon guidance cues. Here we provide the first measurements of Cdc42 activity in living growth cones acutely stimulated with both growth-promoting and growth-inhibiting axon-guidance cues. Interestingly, we find that both permissive and repulsive factors can work by modulating Cdc42 activity, but in opposite directions. We find that the growth-promoting factors laminin and BDNF activate Cdc42, whereas the inhibitor Slit2 reduces Cdc42 activity in growth cones. Remarkably, we find that regulation of focal adhesion kinase (FAK) activity is a common upstream modulator of Cdc42 by BDNF, laminin and Slit. These findings suggest that rapid modulation of Cdc42 signaling through FAK by receptor activation underlies changes in growth cone motility in response to permissive and repulsive guidance cues.

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Language(s): eng - English
 Dates: 2012-06-15
 Publication Status: Issued
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000307767100015
DOI: 10.1242/jcs.100107
 Degree: -

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Title: Journal of Cell Science
Source Genre: Journal
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Publ. Info: Cambridge, U.K. : Co. of Biologists
Pages: - Volume / Issue: 125 (12) Sequence Number: - Start / End Page: 2918 - 2929 Identifier: ISSN: 0021-9533
CoNE: https://pure.mpg.de/cone/journals/resource/954925326678