Protein CutA undergoes an unusual transfer into the secretory pathway and affects the folding, oligomerization, and secretion of acetylcholinesterase.
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.
Liang
Dong
D
Laboratoire de Neurobiologie, CNRS UMR 8544, Ecole Normale Supérieure, 46 Rue d'Ulm, 75005 Paris, France.
Nunes-Tavares
Nilson
N
Xie
Heidi Q
HQ
Carvalho
Stéphanie
S
Bon
Suzanne
S
Massoulié
Jean
J
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D020836:Protein Structure, Quaternary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats
C501043:Cuta protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508016:PRiMA1 protein, rat; D000110:Acetylcholinesterase