severingproteiner

Severingproteiner is a term used to describe a class of cytoskeletal-modifying proteins that cleave filamentous polymers such as actin filaments and microtubules. By severing filaments, they generate new ends that can rapidly depolymerize or elongate, enabling timely remodeling of the cytoskeleton in response to cellular cues. The concept encompasses proteins that act on different filament systems and can have diverse regulatory mechanisms.

Two major functional groups are actin-severing proteiner and microtubule-severing proteiner. Representative actin-severing examples include cofilin/ADF and gelsolin, which bind actin filaments and induce breaks or destabilize filament sides. Representative microtubule-severing examples include katanin, spastin, and fidgetin, which are ATPases of the AAA+ family that sever microtubules and generate fragments that can depolymerize or serve as new seeds for growth.

Mechanistically, actin severing often involves binding to filament lattices, introducing twists, and creating breaks, with activity modulated by calcium levels and nucleotide state of actin. Microtubule severing relies on ATP hydrolysis by hexameric machines to disrupt lateral bonds within the microtubule lattice, producing short fragments that can be rapidly depolymerized or repurposed for polymerization elsewhere.

Functions of severingproteiner include enabling cell migration, cytokinesis, axon and dendrite outgrowth, and remodeling of organelles and the mitotic spindle. Regulation is typically achieved through post-translational modifications, Ca2+, pH, phosphorylation, and interactions with membranes or other cytoskeletal factors, localizing activity to specific cellular regions.

Clinical relevance exists for severingproteiner, with mutations in certain members linked to neurodegenerative diseases and developmental disorders; dysregulation can also influence cancer cell behavior. Ongoing research aims to clarify specific regulatory networks, substrate specificities, and therapeutic potential.