HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mezgrhani, H. Articles by Miquelis, R. Search for Related Content PubMed PubMed Citation Articles by Mezgrhani, H. Articles by Miquelis, R. Social Bookmarking                      What's this?

Volume 272, Number 37, Issue of September 12, 1997 pp. 23340-23346
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of the Membrane Receptor Binding Domain of Thyroglobulin
INSIGHTS INTO QUALITY CONTROL OF THYROGLOBULIN BIOSYNTHESIS

(Received for publication, February 18, 1997, and in revised form, June 6, 1997)

From the Laboratoire de Biochimie, Ingénierie des Protéines, UMR 6560, Institut Fédératif Jean Roche, Faculté de Médecine-Nord, Boulevard P. Dramard, 13916 Marseille Cedex 20, France

The last stages of thyroglobulin maturation occur in the thyroid follicular lumen and include thyroid hormone formation and glycan completion. In this compartment, newly secreted thyroglobulins interact with a thyrocyte membrane receptor that prevents their premature lysosomal transfer and degradation. Both GlcNAc moieties and thyroglobulin peptide determinants are involved in receptor interaction. Here we used monoclonal antibodies (mAbs) directed against human thyroglobulin either to inhibit (mAb78) or to enhance (mAb240) the thyroglobulin binding and to identify the region of the thyroglobulin involved in the receptor recognition.

Peptides containing the mAb epitopes were obtained by immunoscreening cyanogen bromide-derived native human thyroglobulin peptides and a cDNA thyroglobulin expression library. Three peptides, localized in the thyroglobulin N-terminal domain, were obtained. Peptides N1 (Ala¹¹⁴⁸-Gln¹²⁹⁵) and N2 (Ser⁷⁸⁹-Met¹⁰⁰⁸) were recognized by mAb240 and mAb78, respectively. None of them bound the receptor. The third peptide, N3 (Ser⁷⁸⁹-Met¹¹⁷²), (i) overlapped all or part of the N1 and N2 peptide sequences and was recognized by both mAbs, (ii) carried two complex glycans at Asn⁷⁹⁷ and Asn⁹²⁸, of which a subset presented accessible GlcNAc residues, and (iii) inhibited the thyroglobulin binding to FRTL5 cell membrane preparations. The N3 peptide includes tyrosine residues that have been reported to be involved in hormone formation. These results suggest that structural modifications closely associated with hormone formation within this domain act as sensors for the receptor interaction and thus for the intrafollicular retention or lysosomal homing of the prohormone.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Marino and R. T. McCluskey Role of thyroglobulin endocytic pathways in the control of thyroid hormone release Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1295 - C1306. [Abstract] [Full Text] [PDF]

				A. Mezghrani, J. Courageot, J. C. Mani, M. Pugniere, P. Bastiani, and R. Miquelis Protein-disulfide Isomerase (PDI) in FRTL5 Cells. pH-DEPENDENT THYROGLOBULIN/PDI INTERACTIONS DETERMINE A NOVEL PDI FUNCTION IN THE POST-ENDOPLASMIC RETICULUM OF THYROCYTES J. Biol. Chem., January 21, 2000; 275(3): 1920 - 1929. [Abstract] [Full Text] [PDF]