Integrin-cytoskeletal interactions in neuronal growth cones

Christine E. Schmidt, Jianwu Dai, Douglas A. Lauffenburger, Michael P. Sheetz, Alan F. Horwitz

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Development of the nervous system requires that neuronal growth cones, in coordination with growing axons, migrate along precise paths defined by specific extracellular matrix cues until they encounter their targets. Laminin promotes growth cone migration through receptors such as the integrins, but the underlying physical mechanism is poorly understood. We have investigated the cytoskeletal associations and surface dynamics of endogenous β1 integrins in chick dorsal root ganglion growth cones migrating on laminin. A single-beam optical gradient trap was used to place 0.5-μo- diameter polystyrene beads conjugated with anti-β1 integrin monoclonal antibodies at desired locations on the growth cone surface. We found a substantial increase in the stable attachment of these beads, with subsequent slow rearward motion, on the front periphery of the growth cone compared to the base. The surface dynamics of smaller aggregates of integrin were explored by monitoring the temporal and spatial displacements of 40-nm- diameter gold particles coated with anti-β1 integrin antibodies. The small particles were transported preferentially to the growth cone periphery by brief directed excursions interspersed with periods of diffusion. In addition, the leading edge of the growth cone was supported to a greater extent by an actin-dependent cytoskeleton that resisted mechanical tether formation. Such a regional differentiation of the growth cone has not been documented previously and has implications for the mechanism of growth cone migration and guidance.

Original languageEnglish (US)
Pages (from-to)3400-3407
Number of pages8
JournalJournal of Neuroscience
Volume15
Issue number5 I
DOIs
StatePublished - May 1995

Keywords

  • cytoskeleton
  • integrin
  • laser optical trap
  • migration
  • motility
  • nerve growth cone
  • single-particle tracking

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Integrin-cytoskeletal interactions in neuronal growth cones'. Together they form a unique fingerprint.

  • Cite this