Crumbs2 acts as a dynamic cellular sensor triggering stable podocyte cell-matrix anchorage

Mammalian Crumbs proteins 2 (CRB2) and CRB3 are expressed in the kidney, with CRB2 mainly found within podocytes. Here, we focused on the function of CRB2 in podocytes. We investigated the CRB2/CRB3A membrane dynamics at the podocyte-podocyte contact interface in a cell culture model. Traction force microscopy was employed to clarify whether the homophilic CRB2 interactions occur in cis or trans. Live-cell imaging revealed the effects of CRB2 and CRB3A expression on cell migration from the single-cell level to large cellular networks at long space and timescales. We found that CRB2 interacts in trans, but surprisingly does not form stable interconnections. Instead, CRB2 acts as a dynamic sensor for the cellular environment and triggers a massive reorganization of focal adhesions and the actin cytoskeleton upon contact of CRB2-positive cells resulting in a strongly increased cell-matrix anchoring. Cytoskeleton reorganization can also be triggered by CRB3A; however, the increased cell-matrix anchorage is CRB2 specific.