title: ClC-5 does not affect megalin expression and function in the thyroid.
abstract: 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.
authors.affiliation: Molecular Biology Center, University of Hamburg, Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Maritzen
authors.forename: Simonetta
authors.initials: S
authors.lastname: Lisi
authors.forename: Roberta
authors.initials: R
authors.lastname: Botta
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fanelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Viacava
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
authors.forename: Michele
authors.initials: M
authors.lastname: Marinò
mesh_terms: 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
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse