Megalin (gp330): A Putative Endocytic Receptor for Thyroglobulin (Tg)

Author:

Zheng Gang1,Marino Michele1,Zhao Jun1,McCluskey Robert T.1

Affiliation:

1. Pathology Research Laboratory, Massachusetts General Hospital, Harvard Medical School

Abstract

Megalin (gp330) is a large glycoprotein receptor found mainly on a group of absorptive epithelial cells, including renal proximal tubule, epididymal and thyroid cells. Megalin has been shown to bind multiple, unrelated ligands, mainly in vitro, and to mediate endocytosis of ligands in cultured cells. However, physiologic ligands of megalin are largely unknown. In the present study we have demonstrated that purified rat megalin binds rat thyroglobulin (Tg) in solid phase assays, with an estimated Kd of 9.2±0.6 nM. Binding was calcium dependent and was almost completely inhibited by excess Tg, by three megalin ligands—lactoferrin, lipoprotein lipase and apolipoprotein J- and by the receptor associated protein (RAP), which inhibits binding of all megalin ligands. Three anti-megalin antibodies partially inhibited Tg binding to megalin. 125I labeled Tg bound to megalin was released by EDTA and heparin; the released product was shown by SDS-PAGE and autoradiography to be 660 kD (dimeric) Tg. However, an immunoblotting experiment showed binding of megalin both to monomeric (330 kD) and dimeric Tg. We propose that megalin, which is known to mediate ligand endocytosis and is found on the apical surface of thyrocytes, may participate in the endocytosis of Tg from the colloid, a process that is required for hormone release from Tg.

Publisher

The Endocrine Society

Subject

Endocrinology

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