Calpains as Potential Regulators of Microtubule-Associated Cytokinesis: A Cross-Eukaryotic Unifying Hypothesis

Calpains constitute an ancient, extensive family of calcium-dependent cysteine proteases found in some bacteria and most eukaryotes. They are involved in a wide variety of developmental and cellular processes and are implicated in major human diseases, but whether they share an ancestral or broadly conserved cellular role remains unclear. Beyond their core CysPc catalytic domain, calpains contain diverse domain combinations and can be either cytosolic or membrane bound. Here, we develop the hypothesis that both cytosolic and transmembrane calpains may contribute to cytokinesis through positional anchoring and organization of microtubules (MTs). We propose that during plant cell division, the singular transmembrane calpain DEK1 play a role in localizing and organizing the array of cortical MTs from the microtubule organizing center (MTOC) and may thereby position the cell division plane, potentially affecting preprophase band placement and subsequent cell plate formation. Similarly, during cell division in animals, their cytosolic calpains may be involved in setting the point of membrane invagination via their association with membrane-bound proteins. We discuss this novel model for calpain activity in the context of data from the animal and plant literature, as well as of our discovery of putative calpain sequences in both brown and red algal genomes. These findings are consistent with the view that calpains were present early in eukaryotic evolution and diversified alongside distinct modes of cell division. Finally, we consider the possibility that early calpain functions may have been linked to the formation and function of MT arrays in flagella and cilia, from which later roles in cytokinesis might have evolved. This model is intended as a testable framework for future studies of calpain function across eukaryotes.