title: Actoclampin (+)-end-tracking motors: How the pursuit of profilin's role(s) in actin-based motility twice led to the discovery of how cells crawl.
abstract: The path to the discovery of the actoclampins began with efforts to define profilin's role in actin-based pathogen and endosome rocketing. That research identified a set of FPPPP-containing cargo proteins and FPPPP-binding proteins that are consistently stationed within the polymerization zone during episodes of active motility. The very same biophysical clues that forced us to abandon Brownian Ratchet models guided us to the Actoclampin Hypothesis, which asserts that every propulsive filament possesses a (+)-end-tracking motor that generates the forces cells need to crawl. Each actoclampin motor is a multi-arm oligomeric complex, employing one arm to recruit/deliver Profilin•Actin•ATP to a growth-site located at the (+)-end of the lagging subfilament, while a second arm maintains an affinity-modulated binding interaction with the extreme (+)-end of the other subfilament. The alternating actions of these arms define a true molecular motor, the processivity of which explains why propelling filaments maintain full possession of their cargo. The Actoclampin Hypothesis also suggests how the energetics of tracker interactions with the (+)-end determines whether a given actoclampin is a passive (low force-producing) or active (high force-producing) motor, the latter requiring the Gibbs free energy of ATP hydrolysis. Another aim of this review is to acknowledge an earlier notional model that emerged from efforts to comprehend profilin's pivotal role(s) in actin-based cell motility.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Florida College of Medicine, Room R3-126 Academic Research Building, Gainesville, FL 32610-0245, USA. Electronic address: dlpurich@ufl.edu.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Purich
mesh_terms: D000199:Actins / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D008840:Microfilament Proteins / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000502:physiology*; D051304:Profilins / Q000502:physiology*
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D020409:Molecular Motor Proteins; D051304:Profilins