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Volume 271, Number 44, Issue of November 1, 1996 pp. 27645-27651
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Degradation of Distinct Assembly Forms of Immunoglobulin M Occurs in Multiple Sites in Permeabilized B Cells

(Received for publication, June 25, 1996)

From the Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel

Protein degradation is essential for quality control which retains and eliminates abnormal, unfolded, or partially assembled subunits of oligomeric proteins. The localization of this nonlysosomal pre-Golgi degradation to the endoplasmic reticulum (ER) has been mostly deduced from kinetic studies and carbohydrate analyses, while direct evidence for degradation within the ER has been provided by in vitro reconstitution of this process. In this article, we took advantage of the transport incompetence of permeabilized cells to directly demonstrate that the selective degradation of secretory IgM (sIgM) in B lymphocytes is transport-dependent. We show that, upon permeabilization of the plasma membrane with either streptolysin O or digitonin, sIgM is not degraded unless transport is allowed. Nevertheless, upon complete reduction of interchain disulfide bonds with thiols, the free µ heavy chains are degraded by a transport-independent quality control mechanism within the ER. This latter degradation is nonselective to the secretory heavy chain µs, and the membrane heavy chain µm, which is normally displayed on the surface of the B cell, is also eliminated. Moreover, the degradation of free µs is no longer restricted to B lymphocytes, and it takes place also in the ER of plasma cells which normally secrete polymers of sIgM. Conversely, when assembled with the light chain, the degradation is selective to sIgM, is restricted to B lymphocytes, and is a transport-dependent post-ER event.

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