Acetylcholinesterase clustering at the neuromuscular junction involves perlecan and dystroglycan

Formation of the synaptic basal lamina at vertebrate neuromuscular junction involves the accumulation of numerous specialized extracellular matrix mol ecules including a specific form of acetylcholinesterase (AChE), the collag enic-tailed form. The mechanisms responsible for its localization at sites of nerve-muscle contact are not well understood. To understand synaptic ACh E localization, we synthesized a fluorescent conjugate of fasciculin 2, a s nake alpha-neurotoxin that tightly binds to the catalytic subunit, Prelabel ing AChE on the surface of Xenopus muscle cells revealed that preexisting A ChE molecules could be recruited to form clusters that colocalize with acet ylcholine receptors at sites of nerve-muscle contact. Likewise, purified av ian AChE with collagen-like tail, when transplanted to Xenopus muscle cells before the addition of nerves, also accumulated at sites of nerve-muscle c ontact. Using exogenous avian AChE as a marker, we show that the collagenic -tailed form of the enzyme binds to the heparan-sulfate proteoglycan perlec an. which in turn binds to the dystroglycan complex through alpha-dystrogly can. Therefore, the dystroglycan-perlecan complex serves as a cell surface acceptor for AChE, enabling it to be clustered at the synapse by lateral mi gration within the plane of the membrane. A similar mechanism may underlie the initial formation of all specialized basal lamina interposed between ot her cell types.