TY - JOUR
T1 - Src and cortactin promote lamellipodia protrusion and filopodia formation and stability in growth cones
AU - He, Yingpei
AU - Ren, Yuan
AU - Wu, Bingbing
AU - Decourt, Boris
AU - Lee, Aih Cheun
AU - Taylor, Aaron
AU - Suter, Daniel M.
PY - 2015/9/15
Y1 - 2015/9/15
N2 - 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 actindriven protrusion versus retraction. In addition, both proteins promote the formation and stability of actin bundles in filopodia.
AB - 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 actindriven protrusion versus retraction. In addition, both proteins promote the formation and stability of actin bundles in filopodia.
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U2 - 10.1091/mbc.E15-03-0142
DO - 10.1091/mbc.E15-03-0142
M3 - Article
C2 - 26224308
AN - SCOPUS:84942106241
SN - 1059-1524
VL - 26
SP - 3229
EP - 3244
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 18
ER -