Open AccessClaudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis
Author(s) -
Megan R Beggs,
Kennedi Young,
Wanling Pan,
D.M. Oneill,
Matthew Saurette,
Allein Plain,
Juraj Rievaj,
Michael R. Doschak,
Emmanuelle Cordat,
Henrik Dimke,
R. Todd Alexander
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111247118
Subject(s) - claudin , paracellular transport , tight junction , transcellular , homeostasis , calcium metabolism , calcium , reabsorption , microbiology and biotechnology , chemistry , endocrinology , biology , medicine , permeability (electromagnetism) , kidney , biochemistry , membrane
Significance Significant calcium absorption across renal and intestinal epithelia occurs via the paracellular pathway. However, the identity of the paracellular pore involved is unknown. Claudin-2 and claudin-12 contribute paracellular calcium permeability in cell models, but single knockout animals don’t have altered serum calcium or bone mineralization. To investigate this,Cldn2/12 double knockout mice were generated. They display decreased intestinal calcium absorption and renal calcium wasting, resulting in hypocalcemia and markedly reduced bone mineralization. Claudin-2 and claudin-12 don’t physically interact in vitro, and coexpression has an additive effect on calcium permeability. Our work identifies claudin-2 and claudin-12 as important constituents of the paracellular Ca2+ pathway in intestine and kidney enabling calcium transport and highlights their important complementary roles in maintaining calcium homeostasis.