PAK–PIX interactions regulate adhesion dynamics and membrane protrusion to control neurite outgrowth
| Autor: | Timothy M. Gomez, Miguel Santiago-Medina, Kelly A. Gregus |
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| Rok vydání: | 2013 |
| Předmět: |
Neurite
Immunoblotting macromolecular substances Plasma protein binding Extracellular matrix Xenopus laevis Laminin Neurites Animals Guanine Nucleotide Exchange Factors Humans Actin filament polymerization p21-activated kinases Growth cone biology Reverse Transcriptase Polymerase Chain Reaction Cell Biology Immunohistochemistry Cell biology enzymes and coenzymes (carbohydrates) p21-Activated Kinases biology.protein Guanine nucleotide exchange factor biological phenomena cell phenomena and immunity Rho Guanine Nucleotide Exchange Factors Protein Binding Research Article |
| Zdroj: | Journal of Cell Science. 126:1122-1133 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.112607 |
| Popis: | Summary The roles of P21-activated kinase (PAK) in the regulation of axon outgrowth downstream of extracellular matrix (ECM) proteins are poorly understood. Here we show that PAK1–3 and PIX are expressed in the developing spinal cord and differentially localize to point contacts and filopodial tips within motile growth cones. Using a specific interfering peptide called PAK18, we found that axon outgrowth is robustly stimulated on laminin by partial inhibition of PAK–PIX interactions and PAK function, whereas complete inhibition of PAK function stalls axon outgrowth. Furthermore, modest inhibition of PAK–PIX stimulates the assembly and turnover of growth cone point contacts, whereas strong inhibition over-stabilizes adhesions. Point mutations within PAK confirm the importance of PIX binding. Together our data suggest that regulation of PAK–PIX interactions in growth cones controls neurite outgrowth by influencing the activity of several important mediators of actin filament polymerization and retrograde flow, as well as integrin-dependent adhesion to laminin. |
| Databáze: | OpenAIRE |
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