Journal of Neuroscience, Vol 12, 2034-2042, Copyright © 1992 by Society for Neuroscience
Central and peripheral neurite outgrowth differs in preference for heparin-binding versus integrin-binding sequences
PK Haugen, JB McCarthy, KF Roche, LT Furcht and PC Letourneau
Department of Cell Biology, University of Minnesota, Minneapolis 55455.
Neurons of the CNS and PNS differ in their response to fibronectin (FN) and
proteolytic fragments of FN. The 33 kDa C-terminal cell and heparin-
binding fragment of FN, in particular, is a strong promoter of CNS neurite
outgrowth. To define further the neurite-promoting activity of the 33 kDa
fragment, and to investigate further the differences between PNS and CNS
responses to FN and the 33 kDa fragment, we contrasted neurite outgrowth by
CNS and PNS neurons on three synthetic peptides representing sequences from
this fragment of FN: two heparin-binding peptides, FN-C/H I and FN-C/H II
(McCarthy et al., 1990), and an integrin-binding peptide, CS1 (Humphries et
al., 1987). Spinal cord (SC) neurons, from the CNS, differed from dorsal
root ganglion (DRG) neurons, from the PNS, with respect to substratum
preference for heparin-binding versus integrin-binding peptides. SC neurite
outgrowth was greatest on the heparin-binding peptide FN-C/H II, while DRG
neurite outgrowth was greatest on the a4 beta 1 integrin-binding peptide
CS1. To test whether the difference in substratum preference was due to
differences in the molecular mechanism by which SC and DRG neurons interact
with the 33 kDa fragment of FN, anti-beta 1 integrin antibodies and/or
soluble heparin were added to the cultures as potential inhibitors of
integrin-mediated or proteoglycan-mediated interactions with FN. SC neurite
outgrowth was much more sensitive to the effect of heparin than anti-beta 1
integrin, indicating SC neurite outgrowth may involve predominantly a
heparin-sensitive mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)