Thyroglobulin internalized by thyrocytes passes through early and late endosomes

Area of Science:

• Cell Biology
• Endocrinology
• Molecular Biology

Background:

• Thyroglobulin (Tg) is the prohormone for thyroid hormones.
• The intracellular pathway for Tg transport from storage to degradation is not fully understood.
• Lysosomes are the primary sites for proteolytic degradation.

Purpose of the Study:

• To characterize intracellular compartments involved in thyroglobulin (Tg) traffic.
• To investigate the role of endosomes in Tg internalization and degradation.
• To elucidate the pathway of Tg from the follicular lumen to lysosomes.

Main Methods:

• Electron microscope immunogold labeling using antibodies against Tg, cation-independent mannose-6-phosphate receptor (MPR), and arylsulfatase-A (ArS-A).
• Microinjection of Tg-colloidal gold complexes into in vitro reconstituted thyroid follicles (RTF).
• Analysis of intact pig tissue, RTF, and isolated vesicles.

Main Results:

• Three types of endocytic structures were identified: early endosomes (EE), late endosomes (LE), and lysosomes (L), characterized by MPR and ArS-A labeling.
• Tg immunoreactivity was highest in EE, decreased in LE, and was undetectable in L.
• Microinjected Tg-gold complexes were rapidly internalized into EE and subsequently transported to LE and L within 60 minutes.

Conclusions:

• This study provides the first direct evidence for the involvement of endosomal compartments in Tg internalization and degradation.
• Internalized Tg is transported to early endosomes (EE) and then transferred to late endosomes (LE).
• The findings clarify the intracellular trafficking pathway of thyroglobulin for proteolytic processing.