Focal adhesion kinase functions downstream of Sema3A signaling during axonal remodeling

Chacón, Mariola R.; Fernández, Gloria; Rico, Beatriz

doi:10.1016/j.mcn.2010.02.001

Cited by 24 publications

(46 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fak flox/flox (Beggs et al, 2003), NEX-Cre (Goebbels et al, 2006) and NEX-Cre;Fak flox/flox were maintained on a CD1 background and crossed as described previously (Chacón et al, 2010). Animals were handled in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC).…”

Section: Micementioning

confidence: 99%

“…Hippocampal cells from Fak conditional mutant mice (Fak flox/flox ) were cultured in poly-L-lysine (0.5 mg/ml) or poly-L-lysine and laminin (5-10 g/ml) and transfected as previously described (Chacón et al, 2010). The plasmid pCS3-N-WASP:Gfp was generated by polymerase chain reaction (PCR) using as template a vector from (Miki et al, 1998) using the following primers: Fwd, 5Ј-CGGAATTCTCAGTCTTCCCATTCA -TCATC ATCCTCAAAATC-3Ј; and Rev, 5Ј-CCCCCAAGCTTGG -CCCGG GGATGAGCTCCGGCCAGCAGCAG-3Ј.…”

Section: Primary Culture and Transfectionmentioning

confidence: 99%

“…For immunoprecipitation and immunoblotting, cortices including hippocampi from control and Fak mutant mice were processed as described previously (Chacón et al, 2010). To detect in vivo phosphorylation of N-WASP, 0.5 mM pervanadate (orthovanadate, Sigma) was used in the lysis buffer.…”

Section: Immunoprecipitation Immunocytochemistry Immunohistochemistmentioning

confidence: 99%

“…One candidate to mediate such activities is focal adhesion kinase (FAK; PTK2 -Mouse Genome Informatics), a large non-receptor tyrosine kinase protein that is highly enriched in the growth cones of neurons (Chacón et al, 2010;Contestabile et al, 2003;Menegon et al, 1999). FAK plays an important role in axon development (Rico et al, 2004;Robles and Gomez, 2006), and is required for axons to respond to different extracellular cues and adhesion molecules, such as semaphorin 3A (SEMA3A), netrin 1, ephrin A1 and L1 (L1CAM -Mouse Genome Informatics) (Bechara et al, 2008;Chacón et al, 2010;Li et al, 2004;Liu et al, 2004;Ren et al, 2004;Woo et al, 2009). However, it remains unclear how FAK participates in these events.…”

Section: Introductionmentioning

confidence: 99%

“…However, it remains unclear how FAK participates in these events. We previously showed that the actin cross-linking protein alpha-actinin lies downstream of FAK (Chacón et al, 2010), suggesting that FAK might directly relay extracellular information to the actin cytoskeleton during axon remodeling.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Focal adhesion kinase regulates actin nucleation and neuronal filopodia formation during axonal growth

et al. 2012

Self Cite

View full text Add to dashboard Cite

The establishment of neural circuits depends on the ability of axonal growth cones to sense their surrounding environment en route to their target. To achieve this, a coordinated rearrangement of cytoskeleton in response to extracellular cues is essential. Although previous studies have identified different chemotropic and adhesion molecules that influence axonal development, the molecular mechanism by which these signals control the cytoskeleton remains poorly understood. Here, we show that in vivo conditional ablation of the focal adhesion kinase gene (Fak) from mouse hippocampal pyramidal cells impairs axon outgrowth and growth cone morphology during development, which leads to functional defects in neuronal connectivity. Time-lapse recordings and in vitro FRAP analysis indicate that filopodia motility is altered in growth cones lacking FAK, probably owing to deficient actin turnover. We reveal the intracellular pathway that underlies this process and describe how phosphorylation of the actin nucleation-promoting factor N-WASP is required for FAK-dependent filopodia formation. Our study reveals a novel mechanism through which FAK controls filopodia formation and actin nucleation during axonal development.

show abstract

Section: Micementioning

confidence: 99%

Section: Primary Culture and Transfectionmentioning

confidence: 99%

Section: Immunoprecipitation Immunocytochemistry Immunohistochemistmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Focal adhesion kinase regulates actin nucleation and neuronal filopodia formation during axonal growth

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

Repulsive axon guidance cues ephrin‐A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins

2012

View full text Add to dashboard Cite

Axonal growth cones turn away from repulsive guidance cues. This may start with reduced protrusive motility in the region the growth cone leading margin that is closer to the source of repulsive cue. Using explants of E7 chick temporal retina, we examine the effects of two repulsive guidance cues, ephrin-A2 and slit3, on retinal ganglion cell growth cone protrusive activity, total F-actin, free F-actin barbed ends, and the activities (phosphorylation states) of actin regulatory proteins, ADF/cofilin and ERM proteins. Ephrin-A2 rapidly stops protrusive activity simultaneously with reducing F-actin, free barbed ends and the activities of ADF/cofilin and ERM proteins. Slit3 also stops protrusion and reduces the activities of ADF/cofilin and ERM proteins. We interpret these results as indicating that repulsive guidance cues inhibit actin polymerization and actin-membrane linkage to stop protrusive activity. Retrograde F-actin flow withdraws actin to the C-domain, where F-actin bundles interact with myosin II to generate contractile forces that can collapse and retract the growth cone. Our results suggest that common mechanisms are used by repulsive guidance cue to disable growth cone motility and remodel growing axon terminals.

show abstract

Tools for Protein Posttranslational Modifications Analysis: FAK, a Case Study

Fonseca

Voabil

Carvalho

et al. 2013

Mass Spectrometry Data Analysis in Proteomics

View full text Add to dashboard Cite

Recent advances in mass spectrometry have resulted in an exponential increase in annotation of posttranslational modifications (PTMs). Just in the Swiss-Prot Knowledgebase, there are 89,931 of a total of 27 characterized PTM types reported experimentally. A single protein can be dynamically modified during its lifetime for regulation of its function. Considering a PTM can occur at different levels and the number of different PTMs described, the number of possibilities for a single protein is unthinkable. Narrowing the study to a single PTM can be rather unmerited considering that most proteins are heavily modified. Currently crosstalk between PTMs is plentifully reported in the literature. The example of amino acids serine and threonine on one hand and lysine on the other hand, as targets of different modifications, demand a more global analysis approach of a protein. Besides the direct competition for the same amino acid, a PTM can directly or indirectly influence other PTMs in the same protein molecule by for example steric hindrance due to close proximity between the modifications or creation of a binding site such as an SH2 binding domain for protein recruitment and further modifications. Given the complexity of PTMs a number of tools have been developed to archive, analyze, and visualize modifications. VISUALPROT is presented here to demonstrate the usefulness of visualizing all annotated protein features such as amino acid content, domains, amino acid modification sites and single amino acid polymorphisms in a single image. VISUALPROT application is demonstrated for the protein focal adhesion kinase (FAK) as an example. FAK is a highly phosphorylated cytoplasmatic tyrosine kinase comprising different domains and regions. FAK is crucial for integrating signals from integrins and receptor tyrosine kinases in processes such as cell survival, proliferation, and motility.

show abstract

Focal adhesion kinase functions downstream of Sema3A signaling during axonal remodeling

Cited by 24 publications

References 53 publications

Focal adhesion kinase regulates actin nucleation and neuronal filopodia formation during axonal growth

Focal adhesion kinase regulates actin nucleation and neuronal filopodia formation during axonal growth

Repulsive axon guidance cues ephrin‐A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins

Tools for Protein Posttranslational Modifications Analysis: FAK, a Case Study

Contact Info

Product

Resources

About