The Journal of Neuroscience, December 1, 1998, 18(23):9703-9715
Neuronal Receptors Mediating Responses to AntibodyActivated
Laminin-1
Jonathan K.
Ivins1,
Holly
Colognato2,
Jordan A.
Kreidberg3,
Peter D.
Yurchenco2, and
Arthur D.
Lander1
1 Department of Developmental and Cell Biology and the
Developmental Biology Center, University of California at Irvine,
Irvine, California 92697, 2 Department of Pathology and
Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway,
New Jersey 08854, and 3 Divisions of Nephrology and
Developmental and Newborn Biology, Children's Hospital and Department
of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115
Embryonic retinal neurons lose the ability to extend neurites on
laminin-1 (LN-1) with increasing developmental age yet still do so on
other laminin isoforms. However, after treatment of LN-1 with
antibodies to "short-arm" regions or removal of the short arms
proteolytically, LN-1 supports attachment and extension of neurites
even by late embryonic retinal neurons. We have mapped a domain for
antibody-mediated "activation" of LN-1 to the N-terminal end of the
1 chain. Furthermore, we show that the primary receptors used in the
retinal neuron response to "activated" LN-1 are integrins 3
1
and 61; these are the same receptors used by these neurons for
outgrowth on other LN isoforms. Interestingly, 31 is
preferentially involved in neurite outgrowth, whereas 61
preferentially mediates attachment and spreading. However, in cultures
from 3 integrin-deficient mice, 61 mediates retinal ganglion
cell neurite outgrowth and compensates for the absence of 31.
Finally, we show that key features of the retinal neuron response to
LN-1 also characterize neurons of the hippocampus, thalamus, and
cerebral cortex; these include poor response to untreated LN-1,
extensive neurite outgrowth on antibody-activated LN-1 or on fragment
E8, and dependence of this response on integrin 61 and at
least one other long arm-binding 1 integrin. These data suggest that
regulation of LN-1 function via the process of activation could have
important consequences for axonal regeneration. Curiously, the data
also imply that the mechanism of laminin activation involves enhanced
function at sites that cannot be considered cryptic.
Key words:
integrin; retina; neurite outgrowth; extracellular
matrix; laminin; antibody activation; knock-out; VLA-3; VLA-6; retinal ganglion cell
Copyright © 1998 Society for Neuroscience 0270-6474/98/18239703-13$05.00/0
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