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Vol. 14, Issue 7, 2665-2676, July 2003
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*Laboratory of Neurobiology and Genetics, The
Rockefeller University, New York, New York 10021; and
Department of Pharmacology,
MSTP Program, University at Stony Brook, Stony
Brook, New York 11794-8651
Submitted December 18, 2002;
Revised February 12, 2003;
Accepted March 3, 2003
Monitoring Editor: Mark Ginsberg
Laminins are extracellular matrix proteins that participate in neuronal
development, survival, and regeneration. During excitotoxin challenge in the
mouse hippocampus, neuron interaction with laminin-10
(
5,
1,
1) protects against neuronal death. To investigate
how laminin is involved in neuronal viability, we infused laminin-1
(
1,
1,
1) into the mouse hippocampus. This infusion
specifically disrupted the endogenous laminin layer. This disruption was at
least partially due to the interaction of the laminin-1
1 chain with
endogenous laminin-10, because infusion of anti-laminin
1 antibody had
the same effect. The disruption of the laminin layer by laminin-1 1) did not
require the intact protein because infusion of plasmin-digested laminin-1 gave
similar results; 2) was posttranscriptional, because there was no effect on
laminin mRNA expression; and 3) occurred in both
tPA/ and
plasminogen/ mice, indicating
that increased plasmin activity was not responsible. Finally, although
tPA/ mice are normally
resistant to excitotoxin-induced neurodegeneration, disruption of the
endogenous laminin layer by laminin-1 or anti-laminin
1 antibody
renders the tPA/ hippocampal
neurons sensitive to kainate. These results demonstrate that neuron
interactions with the deposited matrix are not necessarily recapitulated by
interactions with soluble components and that the laminin matrix is a dynamic
structure amenable to modification by exogenous molecules.
Corresponding author. E-mail address:
strickland{at}rockefeller.edu.
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