title: PAK-PIX interactions regulate adhesion dynamics and membrane protrusion to control neurite outgrowth.
abstract: 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.
authors: Department of Neuroscience, Neuroscience Training Program, University of Wisconsin, Madison, WI 53706, USA.
authors: Miguel
authors: M
authors: Santiago-Medina
authors: Kelly A
authors: KA
authors: Gregus
authors: Timothy M
authors: TM
authors: Gomez
mesh_terms: D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D016501:Neurites / Q000378:metabolism*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064067:Rho Guanine Nucleotide Exchange Factors; D014982:Xenopus laevis; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D054462:p21-Activated Kinases