Assembly and regulation of acetylcholinesterase at the vertebrate neuromuscular junction.
| Title: | Assembly and regulation of acetylcholinesterase at the vertebrate neuromuscular junction. |
|---|---|
| Authors: | Rotundo RL; Department of Cell Biology and Anatomy, The University of Miami School of Medicine, 1600 N.W. 10th Avenue, Miami, FL 33136, USA. rrotundo@miami.edu; Ruiz CA; Marrero E; Kimbell LM; Rossi SG; Rosenberry T; Darr A; Tsoulfas P |
| Source: | Chemico-biological interactions [Chem Biol Interact] 2008 Sep 25; Vol. 175 (1-3), pp. 26-9. Date of Electronic Publication: 2008 May 27. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0009-2797 (Print) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier; Original Publication: Amsterdam, Elsevier. |
| MeSH Terms: | Acetylcholinesterase/*metabolism ; Neuromuscular Junction/*enzymology; Acetylcholinesterase/genetics ; Elapid Venoms/metabolism ; Molecular Chaperones/metabolism ; RNA-Binding Proteins/metabolism ; Transcription Factors/metabolism ; Animals ; Protein Biosynthesis ; Vertebrates |
| Abstract: | The collagen-tailed form of acetylcholinesterase (ColQ-AChE) is the major if not unique form of the enzyme associated with the neuromuscular junction (NMJ). This enzyme form consists of catalytic and non-catalytic subunits encoded by separate genes, assembled as three enzymatic tetramers attached to the three-stranded collagen-like tail (ColQ). This synaptic form of the enzyme is tightly attached to the basal lamina associated with the glycosaminoglycan perlecan. Fasciculin-2 is a snake toxin that binds tightly to AChE. Localization of junctional AChE on frozen sections of muscle with fluorescent Fasciculin-2 shows that the labeled toxin dissociates with a half-life of about 36 h. The fluorescent toxin can subsequently be taken up by the muscle fibers by endocytosis giving the appearance of enzyme recycling. Newly synthesized AChE molecules undergo a lengthy series of processing events before final transport to the cell surface and association with the synaptic basal lamina. Following co-translational glycosylation the catalytic subunit polypeptide chain interacts with several molecular chaperones, glycosidases and glycosyltransferases to produce a catalytically active enzyme that can subsequently bind to one of two non-catalytic subunits. These molecular chaperones can be rate limiting steps in the assembly process. Treatment of muscle cells with a synthetic peptide containing the PRAD attachment sequence and a KDEL retention signal results in a large increase in assembled and exportable AChE, providing an additional level of post-translational control. Finally, we have found that Pumilio2, a member of the PUF family of RNA-binding proteins, is highly concentrated at the vertebrate neuromuscular junction where it plays an important role in regulating AChE translation through binding to a highly conserved NANOS response element in the 3'-UTR. Together, these studies define several new levels of AChE regulation in electrically excitable cells. |
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| Grant Information: | R01 AG005917 United States AG NIA NIH HHS |
| Substance Nomenclature: | 0 (Elapid Venoms); 0 (Molecular Chaperones); 0 (RNA-Binding Proteins); 0 (Transcription Factors); 0 (pumilio protein, human); 86697-68-9 (fasciculin); EC 3.1.1.7 (Acetylcholinesterase) |
| Entry Date(s): | Date Created: 20080705 Date Completed: 20081210 Latest Revision: 20250529 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC2952421 |
| DOI: | 10.1016/j.cbi.2008.05.025 |
| PMID: | 18599029 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.