Protein CutA Undergoes an Unusual Transfer into the Secretory Pathway and Affects the Folding, Oligomerization, and Secretion of Acetylcholinesterase
Open accessAbstract
The mammalian protein CutA was first discovered in a search for the membrane anchor of mammalian brain acetylcholinesterase (AChE). It was co-purified with AChE, but it is distinct from the real transmembrane anchor protein, PRiMA. CutA is a ubiquitous trimeric protein, homologous to the bacterial CutA1 protein that belongs to an operon involved in resistance to divalent ions ("copper tolerance A"). The function of this protein in plants and animals is unknown, and several hypotheses concerning its subcellular localization have been proposed. We analyzed the expression and the subcellular localization of mouse CutA variants, starting at three in-frame ATG codons, in transfected COS cells. We show that CutA produces 20-kDa (H) and 15-kDa (L) components. The H component is transferred into the secretory pathway and secreted, without cleavage of a signal peptide, whereas the L component is mostly cytosolic. We show that expression of the longer CutA variant reduces the level of AChE, that this effect depends on the AChE C-terminal peptides, and probably results from misfolding. Surprisingly, CutA increased the secretion of a mutant possessing a KDEL motif at its C terminus; it also increased the formation of AChE homotetramers. We found no evidence for a direct interaction between CutA and AChE. The longer CutA variant seems to affect the processing and trafficking of secretory proteins, whereas the shorter one may have a distinct function in the cytoplasm.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CUTA affects the folding, oligomerization, and secretion of acetylcholinesterase.
“CUTA affects the folding, oligomerization, and secretion of acetylcholynesterase91”
From Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders (2017) · cites this paper as [91]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A new and rapid colorimetric determination of acetylcholinesterase activity
Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961) · Biochemical Pharmacology · doi:10.1016/0006-2952(61)90145-9 · Cited by 27,221 · see citing works
Mass Spectrometric Sequencing of Proteins from Silver-Stained Polyacrylamide Gels
Shevchenko, A., Wilm, M. S., Vorm, O., & Mann, M. (1996) · Analytical Chemistry · doi:10.1021/ac950914h · Cited by 8,930 · see citing works
[19] Rapid and efficient site-specific mutagenesis without phenotypic selection
Kunkel, T. A., Roberts, J. D., & Zakour, R. A. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)54085-x · Cited by 5,341 · see citing works
An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs
Kozak, M. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.20.8125 · Cited by 5,090 · see citing works
pEF-BOS, a powerful mammalian expression vector
Mizushima, S., & Nagata, S. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.17.5322 · Cited by 1,632 · see citing works
Perrier, A. L., Massoulié, J., & Krejci, É. (2002) · Neuron · doi:10.1016/s0896-6273(01)00584-0 · Cited by 247 · see citing works
Self-citationDevelopmental regulation of IgM secretion: The role of the carboxy-terminal cysteine
Sitia, R., Neuberger, M. S., Alberini, C. M., Bet, P., Fra, A., Valetti, C., Williams, G. T., & Milstein, C. (1990) · Cell · doi:10.1016/0092-8674(90)90092-s · Cited by 244 · see citing works
Inestrosa, N. C., Roberts, W. L., Marshall, T. L., & Rosenberry, T. L. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61212-8 · Cited by 183 · see citing works
Quaternary Associations of Acetylcholinesterase
Bon, S., Coussen, F., & Massoulié, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.5.3016 · Cited by 128 · see citing works
Self-citationMolecular genetics of a chromosomal locus involved in copper tolerance in Escherichia coli K‐12
Fong, S., Camakaris, J., & Lee, B. T. O. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.tb02286.x · Cited by 112 · see citing works
Legay, C., Bon, S., Vernier, P., Coussen, F., & Massoulié, J. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb05856.x · Cited by 108 · see citing works
Self-citationGrassi, J., Vigny, M., & Massoulié, J. (1982) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1982.tb08651.x · Cited by 107 · see citing works
Self-citationQuaternary Associations of Acetylcholinesterase
Bon, S., & Massoulié, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.5.3007 · Cited by 90 · see citing works
Self-citationOld and new questions about cholinesterases
Massoulié, J., Perrier, N., Noureddine, H., Liang, D., & Bon, S. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.04.039 · Cited by 89 · see citing works
Self-citationGennari, K., Brunner, J., & Brodbeck, U. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb03386.x · Cited by 77 · see citing works
The structure of the PII–ATP complex
Xu, Y., Carr, P. D., Huber, T., et al. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02074.x · Cited by 57 · see citing works
Arnesano, F., Banci, L., Benvenuti, M., Bertini, I., Calderone, V., Mangani, S., & Viezzoli, M. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304398200 · Cited by 54 · see citing works
Tanaka, Y., Tsumoto, K., Nakanishi, T., Yasutake, Y., Sakai, N., Yao, M., Tanaka, I., & Kumagai, I. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01402-9 · Cited by 47 · see citing works
Two Distinct Proteins Are Associated with Tetrameric Acetylcholinesterase on the Cell Surface
Perrier, A. L., Cousin, X., Boschetti, N., Haas, R., Chatel, J., Bon, S., Roberts, W. L., PICKETT, S., Massoulié, J., Rosenberry, T. L., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004289200 · Cited by 43 · see citing works
Self-citationBelbeoc'h, S., Massoulié, J., & Bon, S. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg360 · Cited by 40 · see citing works
Self-citationAcetylcholinesterase H and T Dimers Are Associated through the Same Contact
Morel, N., Leroy, J., Ayon, A., Massoulié, J., & Bon, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103192200 · Cited by 37 · see citing works
Self-citationBelbeoc'h, S., Falasca, C., Leroy, J., Ayon, A., Massoulié, J., & Bon, S. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04052.x · Cited by 33 · see citing works
Self-citationHydrophobic Protein that Copurifies with Human Brain Acetylcholinesterase
Navaratnam, D. S., Fernando, F. S., Priddle, J. D., Giles, K., Clegg, S. M., Pappin, D., Craig, I., & Smith, A. D. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0742146.x · Cited by 29 · see citing works
Noureddine, H., Schmitt, C., Liu, W., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607221200 · Cited by 28 · see citing works
Acetylcholinesterase Associates Differently with Its Anchoring Proteins ColQ and PRiMA
Noureddine, H., Carvalho, S., Schmitt, C., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801364200 · Cited by 25 · see citing works
Self-citationFalasca, C., Perrier, N., Massoulié, J., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409201200 · Cited by 24 · see citing works
Self-citationOverexpression of human CUTA isoform2 enhances the cytotoxicity of copper to HeLa cells.
Yang, J., Li, Q., Yang, H., Yan, L., Yang, L., & Yu, L. (2008) · Acta Biochimica Polonica · doi:10.18388/abp.2008_3089 · Cited by 14 · see citing works
X‐ray crystal structure of CutA from Thermotoga maritima at 1.4 Å resolution
Savchenko, A. V., Skarina, T., Evdokimova, E., Watson, J. D., Laskowski, R. A., Arrowsmith, C. H., Edwards, A. M., Joachimiak, A., & Zhang, R. (2003) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10585 · Cited by 14 · see citing works
Characterization of the human CUTA isoform2 present in the stably transfected HeLa cells
Yang, J., Yang, H., Yan, L., et al. (2007) · Molecular Biology Reports · doi:10.1007/s11033-007-9152-9 · Cited by 9 · see citing works
Lin, C.-H., Chin, K., Gao, F. P., et al. (2006) · Acta Crystallographica Section F Structural Biology and Crystallization Communications · doi:10.1107/s1744309106039832 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The role of copper and the copper-related protein CUTA in mediating APP processing and Aβ generation
Hou, P., Liu, G., Zhao, Y., Shi, Z., Zheng, Q., Bu, G., Xu, H., & Zhang, Y.-W. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.12.005 · Cited by 32 · see citing works
Zhao, Y., Wang, Y., Hu, J., Zhang, X., & Zhang, Y.-W. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.330209 · Cited by 28 · see citing works
Mozzi, A., Forni, D., Cagliani, R., Pozzoli, U., Clerici, M., & Sironi, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-06440-4 · Cited by 19 · see citing works
- Authors
- Liang, D., Nunes-Tavares, N., Xie, H. Q., Carvalho, S., Bon, S., & Massoulié, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Massoulié, Jean
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 284
- Issue
- 8
- Pages
- 5195-5207
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1966655768
- Cited by
- 19
- References
- 30
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2020: 1 · 2017: 1 · 2015: 1 · 2014: 3 · 2012: 3
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- acetylcholinesterase, secretory pathway, protein secretion, protein folding, protein misfolding, oligomerization, subcellular localization, signal peptide, PRIMA, C-terminal peptide, protein trafficking
- MeSH terms
- Acetylcholinesterase, Animals, Chlorocebus aethiops, Membrane Proteins, Nerve Tissue Proteins, Protein Folding, COS Cells, Amino Acid Motifs, Protein Structure, Quaternary, Protein Transport, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
