The NC1 domain of type IV collagen promotes axonal growth in sympathetic neurons through interaction with the α1β1 integrin

Pamela J Lein, Dennis Higgins, David C. Turner, Leonard A. Flier, Victor P. Terranova

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112 Scopus citations


We have examined the effects of collagen IV on the morphological development of embryonic rat sympathetic neurons in vitro. In short-term (≤24 h) culture, collagen IV accelerated process outgrowth, causing increases in the number of neuntes and total neuritic length. Analysis of proteolytic fragments of collagen IV indicated that the NC1 domain was nearly as active as the intact molecule in stimulating process outgrowth; in contrast, the 7S domain and triple helix-rich fragments of collagen IV were inactive. Moreover, anti-NC1 antiserum inhibited neuritic outgrowth on collagen IV by 79%. In long-term (up to 28 d) cultures, neurons chronically exposed to collagen IV maintained a single axon but failed to form dendrites. Thus, the NC1 domain of collagen IV can alter neuronal development by selectively stimulating axonal growth. Comparison of collagen IV's effects to those of laminin revealed that these molecules exert quantitatively different effects on the rate of initial axon growth and the number of axons extended by sympathetic neurons. Moreover, neuritic outgrowth on collagen IV, but not laminin, was blocked by cycloheximide. We also observed differences in the receptors mediating the neurite-promoting activity of these proteins. Two different antisera that recognize β1 integrins each blocked neuritic outgrowth on both collagen IV and laminin; however, an m Ab (3A3) specific for the α1β1 integrin inhibited collagen IV but not laminin-induced process growth in cultures of both sympathetic and dorsal root neurons. These data suggest that immunologically distinct integrins mediate the response of peripheral neurons to collagen IV and laminin.

Original languageEnglish (US)
Pages (from-to)417-428
Number of pages12
JournalJournal of Cell Biology
Issue number2
StatePublished - Apr 1991
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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