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.
Larsson
F
F
Institute of Anatomy and Cell Biology, The Sahlgrenska Academy at Göteborg University, 420, 40530, Sweden. fredrik.larsson@anatcell.gu.se
Fagman
H
H
Nilsson
M
M
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism
D015820:Cadherins; D011989:Receptors, Thyrotropin; D005576:Colforsin; D013972:Thyrotropin; D000242:Cyclic AMP; D002118:Calcium