Major sperm protein

Abstract

What is it? Major sperm protein, commonly referred to as MSP, is the centerpiece of the motility machinery that propels the crawling movement of nematode sperm. MSP was originally identified in Caenorhabditis elegans, but has since been found in sperm from several other species of nematode. The name derives from the abundance and cellular specificity of the 14kDa protein: MSP makes up 15–20% of the total protein in nematode sperm, but is not found in any other cell type in the worm.What does it do? MSP polymerizes into filaments that pack the sperm lamellipod. Worm sperm have no flagellum and move by crawling, like many other metazoan cells. This form of movement is typically associated with the actin cytoskeleton, but in nematode sperm MSP has taken over this role of actin. The sperm nevertheless move just like actin-rich crawling cells by protrusion of the leading edge of the lamellipod coordinated with attachment to the substratum and retraction of the trailing cell body.So MSP must be a lot like actin… Not much. Both proteins self-assemble into filaments, but the similarity ends there. One fundamental different is that, unlike actin, MSP does not bind and hydrolyze ATP. The subunit for MSP polymerization is a structurally symmetric dimer and unlike actin filaments, which assemble from monomers so that they have characteristic barbed and pointed ends, the two ends of an MSP filament are identical and lack the polarity that is so important to the function of actin filaments.So how does the MSP machinery work? The dynamics of the MSP cytoskeleton in sperm are remarkably similar to those exhibited by actin in other crawling cells. Filaments assemble along the leading edge of a moving sperm and are then displaced rearward to the base of the lamellipod, where they are taken apart. Thus, the cytoskeleton lengthens at one end and shortens at the other, and in so doing produces the forces that push the leading edge forward (protrusion) and pull along the cell body (retraction). Both of these processes have been reconstituted in cell-free sperm extracts, where vesicles derived from the sperm plasma membrane trigger the assembly of a columnar meshwork of filaments, called a fiber, which pushes the vesicle forward in the same way that cytoskeletal assembly drives protrusion in vivo. Fibers can also be induced to shorten, mimicking the process that powers cell body retraction in motile sperm.Are there MSP-binding proteins? To date, three have been identified, including an integral membrane protein which, when phosphorylated, orchestrates MSP filament assembly along the lamellipodial leading edge, and two cytosolic proteins, known as MSP fiber proteins (MFP) 1 and 2. MFP 1 decreases the rate of filament assembly in vitro, while MFP 2 has the opposite effect, but the exact functions of these soluble proteins are not yet known. Although the list of MSP binding proteins is not yet complete, the simplicity of this motility system suggests that it may require only a handful of accessory components to operate.What is MSP's phylogenetic range? Proteins with MSP-like domains have been identified, mostly by genomic analysis, in organisms ranging from yeast to humans. These proteins also contain additional domains and, in most cases, their functions are unknown.Does MSP have any other functions? Recent work has shown that MSP functions as a bipartite extracellular signaling molecule that triggers oocyte maturation and stimulates the oviduct wall to move the oocytes into position for fertilization. MSP lacks the sequence motifs typically found in secretory proteins and it is not yet known how the protein exits sperm to influence oocytes.View Large Image | View Hi-Res Image | Download PowerPoint SlideWhat can work on MSP tell us generally about how cells crawl? The motility produced by the MSP and actin machinery is so similar that the two systems can be compared to identify shared properties required for locomotion. Worm sperm are stripped-down cells: the ‘Volkswagen Beetle’ of the crawling cells, built solely to deliver a nucleus for fertilization. Work on MSP has already shown that a cell can crawl effectively using only a simple cytoskeletal assembly-disassembly, push-pull mechanism without requiring molecular motors, elaborate signaling systems, or a complex network of accessory proteins.