Figure 1613

ATP depletion increases the stability of chaperone-folding polypeptide interactions in the endoplasmic reticulum (ER). Immunoglobulin binding protein (BiP), and perhaps other ER molecular chaperones, associate with nascent polypeptides as they are folded and assembled in ER [20, 54, 56, 57, 65-73]. The dissociation of these proteins requires hydrolysis of ATP [69]. Thus, when levels of ATP drop, BiP should not dissociate from the secretory proteins and the normally transient interaction should become more stable. Here, the associations of ER molecular chap-erones with a model ER secretory protein is examined by Western blot analysis of thyroglobulin (Tg) immunoprecipitates from thyroid cells subjected to ATP depletion. After treatment with antimycin A, there is an increase in the amounts of ER molecular chaperones (BiP, grp94 and ERP72) which co-immunoprecipitate with antithyroglobulin antibody [11], suggesting that ATP depletion causes stabilization of the interactions between molecular chaperones and secretory proteins folded and assembled in the ER. Moreover, because a number of proteins critical to the proper functioning of polarized epithelial cells (ie, occludin, E-cadherin, Na-K-ATPase) are folded and assembled in the ER, this suggests that recovery from ischemic injury is likely to depend, at least in part, on the ability of the cell to rescue the protein-folding and -assembly apparatus of the ER. Control media (MED) and phosphate buffered saline (PBS)—no ATP depletion; 1, 5, 10|xM antimycin A—ATP-depleting conditions. (From Kuznetsov et al. [11]; with permission.)

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