Distribution and Function of Laminins in the Neuromuscular System of Developing, Adult, and Mutant Mice
Open Access
- 15 December 1997
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 139 (6), 1507-1521
- https://doi.org/10.1083/jcb.139.6.1507
Abstract
Laminins, heterotrimers of α, β, and γ chains, are prominent constituents of basal laminae (BLs) throughout the body. Previous studies have shown that laminins affect both myogenesis and synaptogenesis in skeletal muscle. Here we have studied the distribution of the 10 known laminin chains in muscle and peripheral nerve, and assayed the ability of several heterotrimers to affect the outgrowth of motor axons. We show that cultured muscle cells express four different α chains (α1, α2, α4, and α5), and that developing muscles incorporate all four into BLs. The portion of the muscle9s BL that occupies the synaptic cleft contains at least three α chains and two β chains, but each is regulated differently. Initially, the α2, α4, α5, and β1 chains are present both extrasynaptically and synaptically, whereas β2 is restricted to synaptic BL from its first appearance. As development proceeds, α2 remains broadly distributed, whereas α4 and α5 are lost from extrasynaptic BL and β1 from synaptic BL. In adults, α4 is restricted to primary synaptic clefts whereas α5 is present in both primary and secondary clefts. Thus, adult extrasynaptic BL is rich in laminin 2 (α2β1γ1), and synaptic BL contains laminins 4 (α2β2γ1), 9 (α4β2γ1), and 11 (α5β2γ1). Likewise, in cultured muscle cells, α2 and β1 are broadly distributed but α5 and β2 are concentrated at acetylcholine receptor–rich “hot spots,” even in the absence of nerves. The endoneurial and perineurial BLs of peripheral nerve also contain distinct laminin chains: α2, β1, γ1, and α4, α5, β2, γ1, respectively. Mutation of the laminin α2 or β2 genes in mice not only leads to loss of the respective chains in both nerve and muscle, but also to coordinate loss and compensatory upregulation of other chains. Notably, loss of β2 from synaptic BL in β2−/− “knockout” mice is accompanied by loss of α5, and decreased levels of α2 in dystrophic α2dy/dy mice are accompanied by compensatory retention of α4. Finally, we show that motor axons respond in distinct ways to different laminin heterotrimers: they grow freely between laminin 1 (α1β1γ1) and laminin 2, fail to cross from laminin 4 to laminin 1, and stop upon contacting laminin 11. The ability of laminin 11 to serve as a stop signal for growing axons explains, in part, axonal behaviors observed at developing and regenerating synapses in vivo.Keywords
This publication has 88 references indexed in Scilit:
- Native chick laminin-4 containing the beta 2 chain (s-laminin) promotes motor axon growth.The Journal of cell biology, 1996
- Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome.The Journal of cell biology, 1996
- Differential expression of laminin polypeptides in developing and adult human kidney.Journal of Histochemistry & Cytochemistry, 1995
- A motoneuron-selective stop signal in the synaptic protein S-lamininNeuron, 1995
- Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches.The Journal of cell biology, 1994
- The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycansNeuron, 1993
- Basement membranes during development of human nerve: Schwann cells and perineurial cells display marked changes in their expression profiles for laminin subunits and ?1 and ?4 integrinsJournal of Neurocytology, 1993
- Distribution of the α1 and α2 chains of collagen IV and of collagens V and VI in Alport syndromeKidney International, 1992
- Purification and Lectin-Binding Properties of s-Laminin, A Synaptic Isoform of the Laminin B1 ChainJournal of Neurochemistry, 1992
- Neurite outgrowth on cryostat sections of innervated and denervated skeletal muscle.The Journal of cell biology, 1987