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© The Rockefeller University Press, 0021-9525/1999//911 $5.00
The Journal of Cell Biology, Volume 145, Number 4, , 1999 911-921

Acetylcholinesterase Clustering at the Neuromuscular Junction Involves Perlecan and Dystroglycan

H. Benjamin Peng^*,, Hongbo Xie^*, Susanna G. Rossi^*,, and Richard L. Rotundo^*,

^* Department of Cell Biology and Anatomy and Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina 27599-7090; and University of Miami School of Medicine, Miami, Florida 33136

Formation of the synaptic basal lamina at vertebrate neuromuscular junction involves the accumulation of numerous specialized extracellular matrix molecules including a specific form of acetylcholinesterase (AChE), the collagenic-tailed form. The mechanisms responsible for its localization at sites of nerve– muscle contact are not well understood. To understand synaptic AChE localization, we synthesized a fluorescent conjugate of fasciculin 2, a snake -neurotoxin that tightly binds to the catalytic subunit. Prelabeling AChE on the surface of Xenopus muscle cells revealed that preexisting AChE molecules could be recruited to form clusters that colocalize with acetylcholine receptors at sites of nerve–muscle contact. Likewise, purified avian AChE with collagen-like tail, when transplanted to Xenopus muscle cells before the addition of nerves, also accumulated at sites of nerve–muscle contact. Using exogenous avian AChE as a marker, we show that the collagenic-tailed form of the enzyme binds to the heparan-sulfate proteoglycan perlecan, which in turn binds to the dystroglycan complex through -dystroglycan. Therefore, the dystroglycan–perlecan complex serves as a cell surface acceptor for AChE, enabling it to be clustered at the synapse by lateral migration within the plane of the membrane. A similar mechanism may underlie the initial formation of all specialized basal lamina interposed between other cell types.

Key Words: acetylcholinesterase (AChE) • neuromuscular junction • perlecan • heparan-sulfate proteoglycan • dystroglycan • basal lamina

Abbreviations used in this paper: AChE, acetylcholinesterase; AChR, acetylcholine receptor; BTX, -bungarotoxin; DG, dystroglycan; ECM, extracellular matrix; HB-GAM, heparin-binding growth-associated molecule; HSPG, heparan-sulfate proteoglycan; MTJ, myotendinous junction; NMJ, neuromuscular junction; OG-BTX, Oregon green-conjugated -bungarotoxin; R-fasciculin 2, tetramethylrhodamine-conjugated fasciculin 2; RU, resonance units.

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