title: Recruitment of the Arp2/3 complex and mena for the stimulation of actin polymerization in growth cones by nerve growth factor.
abstract: The growth of axons and dendrites during development and regeneration is regulated by cues in the environment. Many of these cues regulate the actin cytoskeleton of the protrusive structures (like filopodia) of the growth cone that are essential for detecting and responding to cues. Nerve growth factor, which promotes the formation of protrusive structures, stimulated actin polymerization in rat sympathetic growth cones, resulting within 1-2 min in accumulations of F-actin at the distal edge and in splotches of F-actin farther back. We examined the potential involvement of a protein machinery important in at least certain types of actin polymerization in non-neuronal cells. Members of the Arp2/3 complex, p34-Arc and p21-Arc, heavily concentrated in the early accumulations of F-actin, as did one member of the Ena/VASP family (Mena) but not another (VASP). Retention of Arc proteins at preferred sites of actin polymerization did not require polymerization itself. Growth cones of differentiated PC12 cells were similar to sympathetic growth cones in their response to NGF. Introduction into these cells of a peptide that should block the binding of Ena/VASP family proteins to the protein complex at sites of actin polymerization reduced the formation of splotches and filopodia in response to NGF. These results point to the early involvement of the Arp2/3 complex and the Ena/VASP family in growth factor-stimulated actin polymerization that gives rise to protrusive structures at the growth cone.
authors.affiliation: Department of Pharmacology and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA. djg@columbia.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Goldberg
authors.forename: M S
authors.initials: MS
authors.lastname: Foley
authors.forename: D
authors.initials: D
authors.lastname: Tang
authors.forename: P W
authors.initials: PW
authors.lastname: Grabham
mesh_terms: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; C102176:Enah protein, mouse; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; C092069:activity regulated cytoskeletal-associated protein; D000098662:Vasodilator-Stimulated Phosphoprotein; D020932:Nerve Growth Factor