Fig. 5. Complexity of SD subunit composition and principle of context-dependent dynamics endowed by the associated network of proteins.

A Schematic representation of the hypothetical molecular appearance of the rodent SD before (upper panel; Grahammer et al.⁷) and after interactome analysis (lower panel). Protein constituents are drawn about to scale (using data from literature and databases, as well as from AlphaFold⁵⁹), and illustration was restricted to structurally distinct constituents (legend on the right) to highlight the complexity of the SD and the associated protein network. Sites and order of interaction, as well as structural details of individual network constituents were not intended. B Hypothetical model for context-dependent dynamics introduced into the SD via the associated network of proteins exemplified by the operation and signaling of kinase Mer (MERTK). Briefly, ligand-triggered enzymatic activity may initiate intracellular signaling pathways or direct/indirect structural arrangement(s) required for proper operation of the filtration process via the GBM. Alteration or ablation of this enzymatic activity will lead to increased permeability of the filter finally leading to proteinuria. For further details see text.