Nematode Sperm Motility: Nonpolar Filament Polymerization Mediated by End-Tracking Motors

Abstract

In nematode sperm cell motility, major sperm protein (MSP) filament assembly results in dynamic membrane protrusions in a manner that closely resembles actin-based motility in other eukaryotic cells. Paradoxically, whereas actin-based motility is driven by addition of ATP-bound actin subunits onto actin filament plus-ends located at the cell membrane, MSP dimers assemble from solution into nonpolar filaments that lack a nucleotide binding site. Thus, filament polarity and on-filament ATP hydrolysis, although essential for actin-based motility, appear to be unnecessary for membrane protrusions by MSP. As a potential resolution to this paradox, we propose a model for MSP filament assembly and force generation by MSP filament end-tracking proteins. In this model, ATP hydrolysis drives affinity-modulated, processive interactions between membrane-associated proteins and elongating filament ends. However, in contrast to the "actoclampin" model for actin filament end-tracking motors, ATP activates the tracking protein (or a soluble cofactor) rather than the MSP subunits themselves (in contrast to activation of actin subunits by ATP binding). The MSP end-tracking model predicts properties that are consistent with several key observations of MSP-based motility, including persistent membrane attachment, polymerization of filament ends at the membrane with depolymerization of free-filament ends away from the membrane, as well as a saturating dependence of polymerization rate on the concentration of non-MSP soluble cytoplasmic components.

Analysis of the ENU-3 protein family in nervous system development in C. elegans

“…It can be concluded that K01G5.3 may have a more direct role than ENU-3 and C38D4.1 in modification of the cytoskeleton with a possible role in actin interaction and modulation. It is likely that they are involved in regulating actin formation and turnover similar to the functions of characterized membraneassociated proteins such as fascin, N-WASP and the Arp 2/3 complex (Dickinson & Purich, 2007). This is indicative of the expression pattern of K01G5.3 which showed several thin, finger-like structures protruding from the cell similar to filopodia which consist of actin filaments cross-linked by actin-binding proteins (Hanein, Matsudaira, & DeRosier, 1997).…”

Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective

“…More recently, biochemical kinetics that regulates the biophysical processes of force generation has been incorporated in a model [970]. Besides, an alternative plausible scenario of MSP assembly has been proposed [971] to explain the motility of nematode sperm cells.…”

Cytoskeleton and Cell Motility

“…But, contrary to ATP-driven actin treadmilling, MSPs assemble into apolar filaments and lack a nucleotide binding site for ATP hydrolysis. To power membrane protrusion, it has recently been proposed that motor end-tracking proteins processively polymerize MSP filaments, while keeping the elongating filaments' ends in contact with membrane-associated proteins [177]. For cell progression however, a second force is required, namely a traction force that pulls the cell body forward once the advancing lamellipodium has been anchored to the substrate on which the cell is crawling.…”