Calcium regulates the interplay between the tight junction and epithelial adherens junction at the plasma membrane

Christopher Mendoza; Sai Harsha Nagidi; Kjetil Collett; Jacob Mckell; Dario Mizrachi

doi:10.1002/1873-3468.14252

Calcium regulates the interplay between the tight junction and epithelial adherens junction at the plasma membrane

Christopher Mendoza
, Sai Harsha Nagidi
, Kjetil Collett
, Jacob Mckell
, Dario Mizrachi

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction (AJ) are substructures of the AJC. The interplay between TJ and AJ membrane proteins to assemble the AJC remains unclear. We employed synthetic biology strategies to express the basic membrane elements of a simple AJC—the adhesive extracellular domains of junctional adhesion molecule A (JAM-A), epithelial cadherin, claudin 1, and occludin—to study their interactions. Our results suggest that calcium concentration fluctuations and JAM-A, acting as an interface molecule between the TJ and AJ, orchestrate their interplay. Calcium affects the secondary structure, oligomerization, and binding affinity of homotypic and heterotypic interactions of TJ and AJ components, thus acting as a molecular switch influencing AJC dynamics.

Original language	English
Pages (from-to)	219-231
Number of pages	13
Journal	FEBS Letters
Volume	596
Issue number	2
DOIs	https://doi.org/10.1002/1873-3468.14252
State	Published - 1 Jan 2022
Externally published	Yes

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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abstract = "The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction (AJ) are substructures of the AJC. The interplay between TJ and AJ membrane proteins to assemble the AJC remains unclear. We employed synthetic biology strategies to express the basic membrane elements of a simple AJC{\textemdash}the adhesive extracellular domains of junctional adhesion molecule A (JAM-A), epithelial cadherin, claudin 1, and occludin{\textemdash}to study their interactions. Our results suggest that calcium concentration fluctuations and JAM-A, acting as an interface molecule between the TJ and AJ, orchestrate their interplay. Calcium affects the secondary structure, oligomerization, and binding affinity of homotypic and heterotypic interactions of TJ and AJ components, thus acting as a molecular switch influencing AJC dynamics.",

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T1 - Calcium regulates the interplay between the tight junction and epithelial adherens junction at the plasma membrane

AU - Mendoza, Christopher

AU - Nagidi, Sai Harsha

AU - Collett, Kjetil

AU - Mckell, Jacob

AU - Mizrachi, Dario

PY - 2022/1/1

Y1 - 2022/1/1

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AB - The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction (AJ) are substructures of the AJC. The interplay between TJ and AJ membrane proteins to assemble the AJC remains unclear. We employed synthetic biology strategies to express the basic membrane elements of a simple AJC—the adhesive extracellular domains of junctional adhesion molecule A (JAM-A), epithelial cadherin, claudin 1, and occludin—to study their interactions. Our results suggest that calcium concentration fluctuations and JAM-A, acting as an interface molecule between the TJ and AJ, orchestrate their interplay. Calcium affects the secondary structure, oligomerization, and binding affinity of homotypic and heterotypic interactions of TJ and AJ components, thus acting as a molecular switch influencing AJC dynamics.

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Calcium regulates the interplay between the tight junction and epithelial adherens junction at the plasma membrane

Abstract

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