Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth.
Actin polymerizes near the leading edge of nerve growth cones, and actin filaments show retrograde movement in filopodia and lamellipodia. Linkage between actin filament retrograde flow and cell adhesion molecules (CAMs) in growth cones is thought to be one of the mechanisms for axon outgrowth and guidance. However, the molecular basis for this linkage remains elusive. Here, we show that shootin1 interacts with both actin filament retrograde flow and L1-CAM in axonal growth cones of cultured rat hippocampal neurons, thereby mediating the linkage between them. Impairing this linkage, either by shootin1 RNA interference or disturbing the interaction between shootin1 and actin filament flow, inhibited L1-dependent axon outgrowth, whereas enhancing the linkage by shootin1 overexpression promoted neurite outgrowth. These results strengthen the actin flow-CAM linkage model ("clutch" model) for axon outgrowth and suggest that shootin1 is a key molecule involved in this mechanism.
Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0192, Japan.
Tadayuki
T
Shimada
Michinori
M
Toriyama
Kaori
K
Uemura
Hiroyuki
H
Kamiguchi
Tadao
T
Sugiura
Naoki
N
Watanabe
Naoyuki
N
Inagaki
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002460:Cell Line; D015638:Cytochalasin D / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats
D000199:Actins; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; C514975:Shtn1 protein, rat; D049452:Green Fluorescent Proteins; D015638:Cytochalasin D