Northwestern Medicine investigators have uncovered new insights into how intercellular “glue” functions to enable interactions between cells, as detailed in a study published in Nature Communications.
In order to communicate and transfer cellular cargo, cells within tissues can link together by fusing their cytoskeletons and cell membranes.
These connective structures, called adherens junctions, play important roles in tissue development and renewal, but remain poorly understood, said Sergey Troyanovsky, PhD, professor of Dermatology, of Cell and Developmental Biology and senior author of the study.
“What we have studied here, in simple words, is the glue that connects cells,” said Troyanovsky, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “One of the basic questions here was: ‘What’s first? The two cells make contact and then intracellular machinery responds, or vice versa?”
In the study, Troyanovsky and members of his laboratory observed the formation of adherens junctions in cultured cells using specifically designed mutated cell lines that allowed them to detect early steps of interactions between the cytoskeleton and E-cadherin, the cellular “glue” protein.
They found that before cells make connections via adherens junctions, they create many small cytoskeleton-bound “pre-junctions” on the surface of their membranes. When contact with other cells is made, the pre-junctions begin to mature and form true adherens junctions, according to the study.
Additionally, the investigators found that these “pre-junctions” form through polymerization of the E-cadherin interacting protein called alpha-catenin along the cytoskeleton filaments.
The findings shed new light on basic cellular processes that occur in a wide array of bodily tissues, Troyanovsky said.
“Understanding this process brings us closer to understanding what is going wrong in different diseases,” Troyanovsky said. “For example, the damaging of cell-cell communications is behind skin disease such as eczema, and cell-cell adhesion disease can contribute to cancer and other autoimmune disease.”
Building on these findings, Troyanovsky and his collaborators will continue to study cell-cell interactions and how other types of junctions form.
“This is important because it shows for the first time the exact mechanism of cell-cell contact assembly. But it’s only one mechanism. The next question is whether cells have only this one mechanism for adherens junction formation. Our preliminary data suggests that there are several other strategies which cells can use to build similar adhesion structures,” Troyanovsky said.
Regina Troyanovsky, PhD, a research associate in the Troyanovsky laboratory, was first author of the study.
The study was supported by National Institute of Health Grants AR070166 and GM148571.
