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Updated: Jun 23, 2026

Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands
Published on: May 30, 2017
Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function
Dorothee Günzel1, Marchel Stuiver, P Jaya Kausalya
1Institute of Clinical Physiology, Charité, 12200 Berlin, Germany. dorothee.guenzel@charite.de
Researchers discovered four new claudin-10 splice variants. Some variants affect tight junction function and ion permeability, while others are retained in the endoplasmic reticulum, impacting cell barrier properties.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Claudin-10 (Cldn10) protein exists in two known isoforms (Cldn10a, Cldn10b) due to alternative splicing of exons 1a and 1b.
- Tight junctions are crucial for maintaining cell barrier integrity and regulating paracellular transport.
Purpose of the Study:
- To identify and characterize novel splice variants of claudin-10.
- To investigate the functional impact of these new variants on tight junction localization and ion permeability.
Main Methods:
- Identification and characterization of claudin-10 splice variants in mouse and human cells.
- Transfection of different claudin-10 isoforms into Madin-Darby canine kidney (MDCK) cells.
- Assessment of protein localization via tight junction insertion or endoplasmic reticulum retention.
- Measurement of paracellular permeability (anion and cation) and transepithelial electrical resistance.
Main Results:
- Four new claudin-10 splice variants were identified, including Cldn10a_v1 (alternative splice donor site in exon 1a) and variants lacking exon 4 (Cldn10a_v2, Cldn10a_v3, Cldn10b_v1).
- Cldn10a, Cldn10a_v1, and Cldn10b localized to tight junctions, while exon 4-lacking variants were ER-retained.
- Cldn10a increased anion permeability; Cldn10a_v1 modulated Cldn10a effects.
- Cldn10b significantly decreased resistance and altered cation permeability and selectivity in MDCK-C7 cells, indicating a high field-strength binding site.
Conclusions:
- Novel claudin-10 splice variants exhibit differential localization and functional consequences.
- Specific claudin-10 isoforms play distinct roles in regulating paracellular ion and organic anion transport.
- The functional impact of claudin-10 variants is influenced by the cellular context, including endogenous claudin expression.
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