Shootin1-cortactin interaction mediates signal-force transduction for axon outgrowth.
Motile cells transduce environmental chemical signals into mechanical forces to achieve properly controlled migration. This signal-force transduction is thought to require regulated mechanical coupling between actin filaments (F-actins), which undergo retrograde flow at the cellular leading edge, and cell adhesions via linker "clutch" molecules. However, the molecular machinery mediating this regulatory coupling remains unclear. Here we show that the F-actin binding molecule cortactin directly interacts with a clutch molecule, shootin1, in axonal growth cones, thereby mediating the linkage between F-actin retrograde flow and cell adhesions through L1-CAM. Shootin1-cortactin interaction was enhanced by shootin1 phosphorylation by Pak1, which is activated by the axonal chemoattractant netrin-1. We provide evidence that shootin1-cortactin interaction participates in netrin-1-induced F-actin adhesion coupling and in the promotion of traction forces for axon outgrowth. Under cell signaling, this regulatory F-actin adhesion coupling in growth cones cooperates with actin polymerization for efficient cellular motility.
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Yusuke
Y
Kubo
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Kentarou
K
Baba
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Michinori
M
Toriyama
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Takunori
T
Minegishi
Laboratory of Biomedical Imaging, Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Tadao
T
Sugiura
Mathematical Informatics, Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Satoshi
S
Kozawa
Mathematical Informatics, Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Kazushi
K
Ikeda
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan ninagaki@bs.naist.jp.
Naoyuki
N
Inagaki
D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D051356:Cortactin / Q000378:metabolism*; D020439:Growth Cones / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075388:Netrin-1; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism
D000199:Actins; D051356:Cortactin; C495870:Cttn protein, rat; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617354:Ntn1 protein, rat; C514975:Shtn1 protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C515906:Pak1 protein, rat; D054462:p21-Activated Kinases