Perlecan Helps Keep AChE in Place

Abstract

Acetylcholinesterase (AChE) is expressed by innervated muscles at the site of motor neuron contact and is required for the termination of acetylcholine-mediated neurotransmission. A particular form of AChE that has a collagen tail is preferentially located at the neuromuscular junction (NMJ), but the mechanism by which it is localized to the NMJ is not well understood. Now, Arikawa-Hirasawa et al. have found that a complex extracellular heparan sulfate proteoglycan termed perlecan is required for proper localization of AChE to the synaptic basal lamina of the NMJ. Whereas muscle development, muscle innervation, and NMJ synapse formation were normal in perlecan-deficient mice, very little AChE was detected in the NMJ of the mutant mice. This result was confirmed in fluorescence assays where no AChE was observed in the NMJ of perlecan-deficient mice. However, the absence of perlecan in these mice did not affect their production of AChE mRNA and protein, because no difference in total AChE activity was detected in muscle homogenates from wild-type and perlecan-deficient mice. Nonetheless, perlecan-deficient mice exhibited poor locomotion and respiratory failure. Thus, perlecan appears to be required for the proper extracellular localization of AChE to the NMJ. E. Arikawa-Hirasawa, S. G. Rossi, R. L. Rotundo, Y. Yamada, Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice. Nature Neurosci. 5 , 119-123 (2002). [Online Journal]