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Actin dynamics in growth cone motility and navigation
Author(s) -
Gomez Timothy M.,
Letourneau Paul C.
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12506
Subject(s) - growth cone , filopodia , lamellipodium , microbiology and biotechnology , actin remodeling , actin remodeling of neurons , mdia1 , actin , protein filament , biology , formins , actin binding protein , microfilament , biophysics , chemistry , actin cytoskeleton , cytoskeleton , axon , biochemistry , cell
Motile growth cones lead growing axons through developing tissues to synaptic targets. These behaviors depend on the organization and dynamics of actin filaments that fill the growth cone leading margin [peripheral (P‐) domain]. Actin filament organization in growth cones is regulated by actin‐binding proteins that control all aspects of filament assembly, turnover, interactions with other filaments and cytoplasmic components, and participation in producing mechanical forces. Actin filament polymerization drives protrusion of sensory filopodia and lamellipodia, and actin filament connections to the plasma membrane link the filament network to adhesive contacts of filopodia and lamellipodia with other surfaces. These contacts stabilize protrusions and transduce mechanical forces generated by actomyosin activity into traction that pulls an elongating axon along the path toward its target. Adhesive ligands and extrinsic guidance cues bind growth cone receptors and trigger signaling activities involving Rho GTP ases, kinases, phosphatases, cyclic nucleotides, and [Ca ++ ] fluxes. These signals regulate actin‐binding proteins to locally modulate actin polymerization, interactions, and force transduction to steer the growth cone leading margin toward the sources of attractive cues and away from repellent guidance cues.Actin filament organization in motile growth cone leading margin (peripheral (P‐) domain) is regulated by actin‐binding proteins that control all aspects of filament assembly, turnover, interactions with other filaments or cytoplasmic components, and produce mechanical forces. This Review outlines key aspects of growth cone actin dynamics, as well as the roles of adhesion‐mediating proteins, like integrins, which stabilize actin‐based protrusions and transduce mechanical forces generated by actomyosin activity into traction that pulls an elongating axon along the path toward its target.