Organizing Synapses

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Two articles this week suggest that interactions with extracellular matrix proteins and channels may underlie synaptic organization. Nishimune et al . report that laminin β2, which is concentrated in the basal lamina that extends through the synaptic cleft at the skeletal neuromuscular junction (NMJ), interacted with the voltage-gated calcium channel (VGCC) pore-forming subunits in the presynaptic nerve terminal. VGCC and laminin 9 (a laminin α4,β2,γ1 heterotrimer) coimmunoprecipitated from and could be cross-linked in Torpedo electric organ, a source of concentrated NMJ-like synapses. The interaction was confirmed with the use of cells transfected to express rat VGCC, which bound to laminin 9-coated beads. Beads coated with laminin 9 or the fragment of laminin β2 that bound to VGCC stimulated VGCC clustering of cultured motor neurons. In addition to the clustered VGCC, these were also sites enriched in vesicles and other factors associated with presynaptic differentiation. Examination of mice deficient for β2 laminin ( Lamb2 –/– ) or the Cav2.1 subunit showed decreased NMJ active zones. Emtage et al. examined Caenorhabditis elegans touch receptor neuron organization and touch sensitivity in animals with mutations in genes encoding several extracellular matrix proteins. One of the genes that produced touch-insensitive animals encoded MEC-1, which the authors characterized and determined to be an extracellular matrix protein with multiple epidermal growth factor (EGF) domains and Kunitz domains. MEC-1 and the collagen MEC-5 colocalized with subunits of the degenerin mechanosensory channel complex (MEC-2, MEC-4, and MEC-6) along the touch receptor process. The punctate distribution of the mechanosensory channel complex required MEC-1, because mec-1 null animals had uniform distribution of MEC-4. Furthermore, MEC-1, MEC-4, and MEC-5 positive puncta correspond to positions of attachment of the touch receptor process to the body wall. These extracellular matrix proteins may also play a role in gating of the channel, an idea that requires further analysis. H. Nishimune, J. R. Sanes, S. S. Carlson, A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals. Nature 432 , 580-587 (2004). [Online Journal] L. Emtage, G. Gu, E. Hartwieg, M. Chalfie, Extracellular proteins organize the mechanosensory channel complex in C. elegans touch receptor neurons. Neuron 44 , 795-807 (2004). [Online Journal]