Synaptic laminin prevents glial entry into the synaptic cleft

Abstract

Presynaptic and postsynaptic membranes directly oppose each other at chemical synapses, minimizing the delay in transmitting information across the synaptic cleft. Extrasynaptic neuronal surfaces, in contrast, are almost entirely covered by processes from glial cells1. The exclusion of glial cells from the synaptic cleft, and the long-term stability of synapses, presumably result in large part from the tight adhesion between presynaptic and postsynaptic elements2,3. Here we show that there is another requirement for synaptic maintenance: glial cells of the skeletal neuromuscular synapse, Schwann cells, are actively inhibited from entering the synaptic cleft between the motor nerve terminal and the muscle fibre. One inhibitory component is laminin 11, a heterotrimeric glycoprotein that is concentrated in the synaptic cleft4. Regulation of an inhibitory interaction between glial cells and synaptic cleft components may contribute to synaptic rearrangements, and loss of this inhibition may underlie the loss of synapses that results from injury to the postsynaptic cell5,6,7,8,9,10,11,12.

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Figure 1: Relationship of Schwann cells to the synaptic cleft at innervated and denervated synaptic sites in control (a, c, e) and laminin β2−/− mutant (b, d, f) muscles.
Figure 2: Schwann cells distinguish laminin-β2-deficient from wild-type matrix.
Figure 3: Laminin 11 inhibits process extension by Schwann cells.
Figure 4: Differential inhibition of neurites and Schwann cells by fragments of laminin β2.

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Acknowledgements

We thank J. Cunningham and S. Weng for assistance, Y.-S. Cheng and P. Yurchenco for laminins, J. Lichtman for comments, and J. Liu for participation in preliminary experiments. This work was supported by grants from the NIH and the NSF.

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Correspondence to Joshua R. Sanes.

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Patton, B., Chiu, A. & Sanes, J. Synaptic laminin prevents glial entry into the synaptic cleft. Nature 393, 698–701 (1998). https://doi.org/10.1038/31502

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