Motor neurons and Schwann cells distinguish between synaptic and extrasynaptic isoforms of laminin.
Laminin is a major component of all basement membranes. However, its composition varies with location because there are numerous forms of each of the three chains (alpha, beta, and gamma) that together comprise this heterotrimeric molecule. In the neuromuscular system, motor neurons and Schwann cells encounter unique trimers of laminin at different sites. The question thus arises as to whether these local differences in laminin composition act to direct the behavior of these two classes of cells. To address this question, we compared the responses of cultured rat motor neurons and Schwann cells to three forms of rodent laminin purified in our laboratory: Laminin-1 (Lmn-1; alpha1beta1gamma1); Laminin-11 (Lmn-11), a synapse-specific isoform consisting of alpha5beta2gamma1 chains; and a third preparation, a mixture of three kinds of laminin (Lmn-2/4/8), that is enriched for the alpha2, alpha4, beta1, beta2, and gamma1 subunits. Schwann cells attached best to a substrate of Lmn-2/4/8 and showed the weakest adhesion on Lmn-11. Interestingly, no such difference was seen with motor neurons; all three substrates promoted neuronal adhesion, survival, and neurite initiation equally well. With longer time in culture, however, these embryonic motor neurons extended extremely long processes on Lmn-1 and on Lmn-2/4/8, while those on Lmn-11 bore shorter neurites with unusually large, flattened growth cones. These results demonstrate that the behavior of Schwann cells and motor neurons can be regulated directly by the local laminin composition. The precise geometric relationship of these cells at the neuromuscular junction may therefore reflect the unique composition of laminin at this synapse.
Cho
S I
SI
Division of Neuroscience, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Ko
J
J
Patton
B L
BL
Sanes
J R
JR
Chiu
A Y
AY
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis*; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016501:Neurites / Q000737:chemistry; D009469:Neuromuscular Junction / Q000737:chemistry; D020033:Protein Isoforms / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology*; D013569:Synapses / Q000737:chemistry*
D007797:Laminin; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms