Proposed core role for cytosolic and transmembrane calpain cysteine proteases in mitotic cell divisions

Abstract 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, yet it remains to be seen if they have a common core function explaining their widespread and varied presence across taxa. Beyond their core CysPc catalytic domain, calpains contain diverse domain combinations and can be either cytosolic or membrane bound. Here we hypothesize a general role for both cytosolic and transmembrane calpains in cellular cytokinesis through positional anchoring and organization of microtubules (MTs). We propose that during plant cell division, the singular transmembrane calpain DEK1 localizes and organizes the array of cortical MTs from the microtubule organizing center (MTOC) to establish the location of the preprophase band and/or the site of cell plate formation according to the positional activation of DEK1 proteins in the nuclear membrane. Similarly, during cell division in animals, their calpains may be involved in setting the point of membrane invagination via their association with membrane-bound proteins. This proposition adds to the current picture of animal MTOC/centrosome function and suggests how a calcium peak during the initial cytokinetic furrowing might be transmitted. We discuss this novel mechanistic model for calpain activity in the context of data from the animal and plant literature, as well as of our novel discovery here of calpain sequences in both brown and red algal genomes. Finally, we speculate that the ancestral role of calpains in early eukaryotes, before the split into the major eukaryotic supergroups, may have been to facilitate the formation and function of MT arrays in flagella and cilia. From this origin, calpains may have developed new functions in eukaryote cell division processes by anchoring centrosomes/MTOC to set the cell division orientations that are especially important for complex multicellularity. Competing Interest Statement The authors have declared no competing interest.