title: Design of active transport must be highly intricate: a possible role of myosin and Ena/VASP for G-actin transport in filopodia.
abstract: Recent modeling of filopodia--the actin-based cell organelles employed for sensing and motility--reveals that one of the key limiting factors of filopodial length is diffusional transport of G-actin monomers to the polymerizing barbed ends. We have explored the possibility of active transport of G-actin by myosin motors, which would be an expected biological response to overcome the limitation of a diffusion-based process. We found that in a straightforward implementation of active transport the increase in length was unimpressive, < or = 30%, due to sequestering of G-actin by freely diffusing motors. However, artificially removing motor sequestration reactions led to approximately threefold increases in filopodial length, with the transport being mainly limited by the motors failing to detach from the filaments near the tip, clogging the cooperative conveyer belt dynamics. Making motors sterically transparent led to a qualitative change of the dynamics to a different regime of steady growth without a stationary length. Having identified sequestration and clogging as ubiquitous constraints to motor-driven transport, we devised and tested a speculative means to sidestep these limitations in filopodia by employing cross-linking and putative scaffolding roles of Ena/VASP proteins. We conclude that a naïve design of molecular-motor-based active transport would almost always be inefficient--an intricately organized kinetic scheme, with finely tuned rate constants, is required to achieve high-flux transport.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Zhuravlev
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Der
authors.forename: Garegin A
authors.initials: GA
authors.lastname: Papoian
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D009218:Myosins
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