title: Src and cortactin promote lamellipodia protrusion and filopodia formation and stability in growth cones.
abstract: Src tyrosine kinases have been implicated in axonal growth and guidance; however, the underlying cellular mechanisms are not well understood. Specifically, it is unclear which aspects of actin organization and dynamics are regulated by Src in neuronal growth cones. Here, we investigated the function of Src2 and one of its substrates, cortactin, in lamellipodia and filopodia of Aplysia growth cones. We found that up-regulation of Src2 activation state or cortactin increased lamellipodial length, protrusion time, and actin network density, whereas down-regulation had opposite effects. Furthermore, Src2 or cortactin up-regulation increased filopodial density, length, and protrusion time, whereas down-regulation promoted lateral movements of filopodia. Fluorescent speckle microscopy revealed that rates of actin assembly and retrograde flow were not affected in either case. In summary, our results support a model in which Src and cortactin regulate growth cone motility by increasing actin network density and protrusion persistence of lamellipodia by controlling the state of actin-driven protrusion versus retraction. In addition, both proteins promote the formation and stability of actin bundles in filopodia.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: Yingpei
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: Boris
authors.initials: B
authors.lastname: Decourt
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: Aih Cheun
authors.initials: AC
authors.lastname: Lee
authors.affiliation: Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907.
authors.forename: Aaron
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907 Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907 dsuter@purdue.edu).
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Suter
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001048:Aplysia / Q000166:cytology* / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured; D051356:Cortactin / Q000378:metabolism*; D015536:Down-Regulation; D020439:Growth Cones / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D051356:Cortactin; D019061:src-Family Kinases