Antenna Mechanism of Length Control of Actin Cables

Abstract

Actin cables are linear cytoskeletal structures that serve as tracks for myosin-based intracellular transport of vesicles and organelles in both yeast and mammalian cells. In a yeast cell undergoing budding, cables are in constant dynamic turnover yet some cables grow from the bud neck toward the back of the mother cell until their length roughly equals the diameter of the mother cell. This raises the question: how is the length of these cables controlled? Here we describe a novel molecular mechanism for cable length control inspired by recent experimental observations in cells. This “antenna mechanism” involves three key proteins: formins, which polymerize actin, Smy1 proteins, which bind formins and inhibit actin polymerization, and myosin motors, which deliver Smy1 to formins, leading to a length-dependent actin polymerization rate. We compute the probability distribution of cable lengths as a function of several experimentally tuneable parameters such as the formin-binding affinity of Smy1 and the concentration of myosin motors delivering Smy1. These results provide testable predictions of the antenna mechanism of actin-cable length control.

The Limiting-Pool Mechanism Fails to Control the Size of Multiple Organelles

“…Our analysis describes the limitations associated with the limiting-pool mechanism and underlines the necessity for the cell to invest in additional mechanisms to control size. In fact, there are other length-sensing mechanisms that have been reported in the filament literature (Andrianantoandro and Pollard, 2006; Chesarone-Cataldo et al, 2011; Gardner et al, 2011; Marshall et al, 2005; Mohapatra et al, 2015, 2016; Varga et al, 2006). In these studies specific proteins have been identified as being critical to length-control, and found to either modulate the assembly or the disassembly rate of cytoskeletal filaments in a length dependent fashion (Mohapatra et al, 2016).…”

“…Indeed, several actin and formin binding proteins have been shown to play an important role in controlling cable length (Chesarone-Cataldo et al, 2011; Mohapatra et al, 2015, 2016). …”

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces

“…Another example is the antenna model in which motors or cross-linkers that antagonize microtubule growth bind with a rate that increases with polymer length [99] . Antenna mechanisms have been proposed to control spindle length [99] , center the chromosomes within the spindle [100,101] , regulate the overlap length of polar microtubules [102] , and to control the length of actin cables in budding yeast [103] . The precision of length control is ultimately limited by the number of associated molecules, e.g.…”

Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast

“…We did not explicitly account for the activation/inactivation of Bnr1formins by Bud14 that displaces the Bnr1 FH2 domain from the barbed ends and thus influences filament length and actin cable structures [Chesarone et al 2009]. Smy1 controls Bnr1 polymerization rate in a cable length dependent manner [Chesarone-Cataldo et al 2011; Mohapatra et al 2015]. This feedback was not modeled here, although the overall effects of Smy1 were considered.…”