The Journal of Immunology, Vol 152, Issue 9 4397-4406, Copyright © 1994 by American Association of Immunologists

ARTICLES

A mutation of the mu transmembrane that disrupts endoplasmic reticulum retention. Effects on association with accessory proteins and signal transduction

TL Stevens, JH Blum, SP Foy, L Matsuuchi and AL DeFranco
Department of Biochemistry, University of California, San Francisco 94143.

The mu heavy chain has an unusually high content of hydroxyl-containing amino acids in its membrane-spanning region. We have examined the involvement of two of these hydrophilic residues in endoplasmic reticulum (ER) retention, interactions with Ig-alpha/Ig-beta, and transmembrane signaling. Neighboring tyrosine and serine residues were mutated to either phenylalanine and alanine (mutant YS/FA) or valine and valine (mutant YS/VV). Membrane Ig (mIgM) molecules containing these mutant mu chains were expressed on the surface of transfected B lymphoma cells. Anti-Ig-induced signaling by the YS/FA mutant mIgM was equivalent to wild-type (wt) mIgM, whereas signaling by the YS/VV mutant mIgM was notably diminished. Association between mutant YS/VV mIgM and Ig-alpha/Ig-beta was detectable but reduced in comparison to YS/FA or wt mIgM. Signaling by YS/VV mutant mIgM appeared to involve Ig- alpha/Ig-beta, because these proteins were tyrosine phosphorylated on receptor cross-linking. When YS/VV and wt mu chains were cotransfected with light chains into nonlymphoid cells, mutant mIgM was expressed at the cell surface in the absence of Ig-alpha/Ig-beta, whereas wt mIgM was not. These data suggest that the mutated residues contribute to ER retention and directly or indirectly to association with Ig-alpha/Ig- beta. Moreover, ER retention can be disrupted without preventing functional association with Ig-alpha/Ig-beta. In addition, these data indicate that the hydroxyl groups of the mutated residues are not required for functional association between mu and Ig-alpha/Ig-beta because their removal did not reduce the ability of the YS/FA mutant mIgM to associate with accessory proteins or to participate in signal transduction.

This article has been cited by other articles:

				F. B. Guloglu and C. A. J. Roman Precursor B Cell Receptor Signaling Activity Can Be Uncoupled from Surface Expression. J. Immunol., June 1, 2006; 176(11): 6862 - 6872. [Abstract] [Full Text] [PDF]

				M. Kremyanskaya and J. G. Monroe Ig-Independent Ig{beta} Expression on the Surface of B Lymphocytes after B Cell Receptor Aggregation J. Immunol., February 1, 2005; 174(3): 1501 - 1506. [Abstract] [Full Text] [PDF]

				W. W. A. Schamel, S. Kuppig, B. Becker, K. Gimborn, H.-P. Hauri, and M. Reth A high-molecular-weight complex of membrane proteins BAP29/BAP31 is involved in the retention of membrane-bound IgD in the endoplasmic reticulum PNAS, August 19, 2003; 100(17): 9861 - 9866. [Abstract] [Full Text] [PDF]

				S. Kunjibettu, S. Fuller-Espie, G. B. Carey, and L. M. Spain Conserved transmembrane tyrosine residues of the TCR {beta} chain are required for TCR expression and function in primary T cells and hybridomas Int. Immunol., February 1, 2001; 13(2): 211 - 222. [Abstract] [Full Text] [PDF]

				C. Condon, S. L. Hourihane, M. Dang-Lawson, J. Escribano, and L. Matsuuchi Aberrant Trafficking of the B Cell Receptor Ig-{alpha}{beta} Subunit in a B Lymphoma Cell Line J. Immunol., August 1, 2000; 165(3): 1427 - 1437. [Abstract] [Full Text] [PDF]

				L. Ellgaard, M. Molinari, and A. Helenius Setting the Standards: Quality Control in the Secretory Pathway Science, December 3, 1999; 286(5446): 1882 - 1888. [Abstract] [Full Text]

				K.-J. Liu, M. Schwen, P. W. Tucker, and B. S. Kim Hybrid Membrane IgM with the Transmembrane Region of I-A{alpha} Facilitates Enhanced Presentation of Distinct Epitopes to T Cells J. Immunol., May 1, 1998; 160(9): 4161 - 4168. [Abstract] [Full Text] [PDF]

				P. Weiser, R. Müller, U. Braun, and M. Reth Endosomal Targeting by the Cytoplasmic Tail of Membrane Immunoglobulin Science, April 18, 1997; 276(5311): 407 - 409. [Abstract] [Full Text]

				G. Rodriguez-Tarduchy, A. G. Sahuquillo, B. Alarcon, and R. Bragado Apoptosis but Not Other Activation Events Is Inhibited by a Mutation in the Transmembrane Domain of T Cell Receptor beta That Impairs CD3zeta Association J. Biol. Chem., November 29, 1996; 271(48): 30417 - 30425. [Abstract] [Full Text] [PDF]