TSH receptor signaling via cyclic AMP inhibits cell surface degradation and internalization of E-cadherin in pig thyroid epithelium.

• Incorporation of E-cadherin into the adherens junction is a highly regulated process required to establish firm cell-cell adhesion in most epithelia. Less is known about the mechanisms that govern the clearance of E-cadherin from the cell surface in both normal and pathological states. In this study, we found that the steady-state removal of E-cadherin in primary cultured pig thyroid cell monolayers is slow and involves intracellular degradation. Experimental abrogation of adhesion by a Ca2+ switch induces rapid cell surface proteolysis of E-cadherin. At the same time, endocytosed intact E-cadherin and newly synthesized E-cadherin accumulate in intracellular compartments that largely escape further degradation. Acute stimulation with thyroid-stimulating hormone (TSH) or forskolin prevents all signs of accelerated E-cadherin turnover. The findings indicate that TSH receptor signaling via cyclic AMP stabilizes the assembly and retention of E-cadherin at the cell surface. This suggests a new mechanism by which TSH supports maintenance of thyroid follicular integrity.

Keyword

Animals

Cadherins

genetics

metabolism

Calcium

metabolism

Cyclic AMP

metabolism

Epithelium

metabolism

Forskolin

metabolism

Receptors

Thyrotropin

metabolism

Signal Transduction

physiology

Swine

Thyroid Gland

metabolism

Thyrotropin

metabolism

Publication and Content Type

ref (subject category)

art (subject category)