ClC-5 does not affect megalin expression and function in the thyroid.
Megalin is an endocytic receptor responsible for thyroglobulin (Tg) transcytosis, a process that favors hormone release. Accordingly, megalin KO mice have primary hypothyroidism. In the kidney, megalin expression is reduced when the gene encoding the chloride transporter ClC-5 is mutated. We investigated whether megalin expression and function in the thyroid are affected by ClC-5 using a ClC-5 KO mouse model. By Western blotting, ClC-5 was found in thyroid tissue extracts of WT, but not of ClC-5 KO mice. In addition, ClC-5 was found to be expressed by cultured thyroid cells (FRTL-5). The thyroid size, weight, and histology were similar in ClC- 5 KO and WT mice, as were the amounts of megalin in thyroid extracts. Accordingly, serum Tg, a measure of megalin-mediated transcytosis, was similar in WT and ClC-5 KO mice, suggesting that megalin function was unaffected. Thus, unlike in megalin KO mice, in ClC-5 KO mice thyroid function was unchanged, as indicated by the normal serum FT4 and TSH. We concluded that in the thyroid, unlike in the kidney, ClC-5 does not affect megalin expression and function, suggesting that megalin is differentially regulated in these two organs.
Maritzen
Tanja
T
Molecular Biology Center, University of Hamburg, Hamburg, Germany.
Lisi
Simonetta
S
Botta
Roberta
R
Pinchera
Aldo
A
Fanelli
Giovanni
G
Viacava
Paolo
P
Marcocci
Claudio
C
Marinò
Michele
M
D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000096:biosynthesis* / Q000235:genetics*; D004705:Endocytosis; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D007668:Kidney / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology
C097503:CLC-5 chloride channel; D018118:Chloride Channels; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse