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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Santiago-Medina M,Gregus KA,Gomez TM

doi

10.1242/jcs.112607

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

1122-33

issue

Pt 5

eissn

0021-9533

issn

1477-9137

pii

jcs.112607

journal_volume

126

pub_type

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