C-terminal and Heparin-binding Domains of Collagenic Tail Subunit Are Both Essential for Anchoring Acetylcholinesterase at the Synapse

Lewis M. Kimbell, Kinji Ohno, Andrew G. Engel, Richard L. Rotundo

Research output: Contribution to journalArticle

71 Scopus citations


The collagen-tailed form of acetylcholinesterase (A12-AChE) appears to be localized at the neuromuscular junction in association with the transmembrane dystroglycan complex through binding of its collagenic tail (ColQ) to the proteoglycan perlecan. The heparan sulfate binding domains (HSBD) of ColQ are thought to be involved in anchoring ColQ to the synaptic basal lamina. The C-terminal domain (CTD) of ColQ is also likely involved, but there has been no direct evidence. Mutations in COLQ cause endplate AChE deficiency in humans. Nine previously reported and three novel mutations are in CTD of ColQ, and most CTD mutations do not abrogate formation of A12-AChE in transfected COS cells. Patient endplates, however, are devoid of AChE, suggesting that CTD mutations affect anchoring of ColQ to the synaptic basal lamina. Based on our observations that purified AChE can be transplanted to the heterologous frog neuromuscular junction, we tested insertion competence of nine naturally occurring CTD mutants and two artificial HSBD mutants. Wild-type human A 12-AChE inserted into the frog neuromuscular junction, whereas six CTD mutants and two HSBD mutants did not. Our studies establish that the CTD mutations indeed compromise anchoring of ColQ and that both HSBD and CTD are essential for anchoring ColQ to the synaptic basal lamina.

Original languageEnglish (US)
Pages (from-to)10997-11005
Number of pages9
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Mar 19 2004


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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