Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin)

• Published in: The Journal of biological chemistry 1993-05, Vol.268 (13), p.9585-9592
• Main Authors: DAVID, V, HOCHSTENBACH, F, SUMATI RAJAGOPALAN, BRENNER, M. B
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Biological and medical sciences; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Calnexin; Cell Line; chaperone; Cloning, Molecular; Dogs; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Female; function; Fundamental and applied biological sciences. Psychology; Gene Library; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Histocompatibility Antigens Class I - genetics; Humans; interaction; Macromolecular Substances; man; Membrane Proteins - genetics; Methionine - metabolism; Miscellaneous; Molecular Sequence Data; Phosphoproteins - genetics; Phosphoproteins - metabolism; Placenta - metabolism; Pregnancy; Proteins; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, T-Cell - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)98391-2

A cDNA clone encoding the human endoplasmic reticulum (ER) resident protein IP90 was isolated and sequenced. It predicts a transmembrane protein with a large ER luminal region showing sequence similarity to calreticulin and a short cytoplasmic domain containing a COOH-terminal RKPRRE sequence that may be relevant to its retention in the ER. It is 95% homologous to the canine ER membrane phosphorprotein called pp90 or calnexin (Wada, I., Rindress, D., Cameron, P. H., Ou, W.-J., Doherty, J. J., II, Louvard, D., Bell, A. W., Dignard, D., Thomas, D. Y., and Bergeron, J. J. M. (1991) J. Biol. Chem. 266, 19599-19610). Previously, in lymphocytes, we have characterized IP90 as a protein associated with partially assembled multichain proteins including the T cell receptor, the membrane immunoglobulin, and the heavy chain of the major histocompatibility complex class I molecules (Hochstenbach, F., David, V., Watkins, S., and Brenner, M. B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4734-4738). Here, we show that within a short metabolic labeling period, IP90 associates transiently with many different newly synthesized proteins. However, in a T cell line that cannot assemble a complete T cell receptor because it lacks the alpha subunit, the unassembled T cell receptor beta chains, which are retained in the ER, remain associated with IP90 throughout a prolonged chase time period. Together, these data offer further evidence suggesting that IP90 may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits.