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Originally published as MBC in Press, 10.1091/mbc.E02-12-0832 on March 20, 2003

Vol. 14, Issue 7, 2665-2676, July 2003

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The Hippocampal Laminin Matrix Is Dynamic and Critical for Neuronal Survival

Zu-Lin Chen *, Justin A. Indyk {dagger} {ddagger}, and Sidney Strickland * §

*Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, New York 10021; and {dagger}Department of Pharmacology, {ddagger}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 ({alpha}5,{beta}1,{gamma}1) protects against neuronal death. To investigate how laminin is involved in neuronal viability, we infused laminin-1 ({alpha}1,{beta}1,{gamma}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 {gamma}1 chain with endogenous laminin-10, because infusion of anti-laminin {gamma}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 {gamma}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.


Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E02–12–0832. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E02-12-0832.

§ Corresponding author. E-mail address: strickland{at}rockefeller.edu.




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