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Mucin 1 is Necessary for TrpV5 Localization in the Kidney's Distal Convoluted Tubule and Normal Bone Architecture
Author(s) -
Ray Evan C.,
AlBataineh Mohammad,
Marciszyn Allison L.,
Poland Paul,
Santucci Christopher,
Robinson Lisa,
Blair Harry C.,
Hughey Rebecca P.,
Kleyman Thomas R.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.862.10
Subject(s) - muc1 , mucin , endocrinology , medicine , homeostasis , reabsorption , chemistry , kidney , distal convoluted tubule , renal physiology , microbiology and biotechnology , biology , biochemistry
Mucin 1 (Muc1 in mice and MUC1 in humans) is a heavily glycosylated transmembrane protein expressed in numerous epithelia. Muc1 interacts with other glycoproteins via interaction with galectins, which bind β‐galactoside sugars. Genome‐wide association data suggest a link between MUC1 polymorphism and bone density. MUC1 exogenously expressed in cultured cells physically interacts with calcium‐selective ion channel TRPV5, increasing cell surface expression and activity in a galectin 3‐dependent fashion. TrpV5 knock‐out (KO) mice exhibit impaired reabsorption of filtered Ca 2+ in the kidney's distal convoluted tubule (DCT), resulting in hypercalciuria and diminished trabecular and cortical bone thickness. We hypothesize that interaction between Muc1 and TrpV5 is necessary for normal Ca 2+ homeostasis and bone architecture. We examined density and architecture in Muc1 KO mice using μCT of lumbar vertebrae. Male Muc1 KO mice exhibit reduced lumbar vertebral cortical and trabecular thickness, with increased surface area/volume. Muc1 KO mice exhibit similar whole‐blood ionized Ca 2+ levels, but increased kidney 1‐α‐hydroxylase levels, suggestive of bodily Ca 2+ depletion. We observe that TrpV5 is mis‐localized in the DCT of Muc1 KO mice, suggesting that impaired renal tubular Ca 2+ reabsorption may contribute to this Ca 2+ depletion. Additionally, TrpV5 is mis‐localized in the DCT in galectin‐3 KO mice, consistent with a role for galectin 3 in mediating Muc1‐TrpV5 interaction. Taken together, these findings suggest that Muc1 plays a role in bodily Ca 2+ homeostasis and bone physiology by enhancing cell surface expression of TrpV5. Support or Funding Information NIDDK K08 DK110332, K01 DK109038, P30 DK079307 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .