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Diverse Functions of Myosin VI in Spermiogenesis

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Diverse Functions of Myosin VI in Spermiogenesis Histochemistry and Cell Biology (2021) 155:323–340 https://doi.org/10.1007/s00418-020-01954-x REVIEW Diverse functions of myosin VI in spermiogenesis Przemysław Zakrzewski1,3 · Marta Lenartowska1,2 · Folma Buss3 Accepted: 2 December 2020 / Published online: 2 January 2021 © The Author(s) 2020 Abstract Spermiogenesis is the fnal stage of spermatogenesis, a diferentiation process during which unpolarized spermatids undergo excessive remodeling that results in the formation of sperm. The actin cytoskeleton and associated actin-binding proteins play crucial roles during this process regulating organelle or vesicle delivery/segregation and forming unique testicular structures involved in spermatid remodeling. In addition, several myosin motor proteins including MYO6 generate force and movement during sperm diferentiation. MYO6 is highly unusual as it moves towards the minus end of actin flaments in the opposite direction to other myosin motors. This specialized feature of MYO6 may explain the many proposed func- tions of this myosin in a wide array of cellular processes in animal cells, including endocytosis, secretion, stabilization of the Golgi complex, and regulation of actin dynamics. These diverse roles of MYO6 are mediated by a range of specialized cargo-adaptor proteins that link this myosin to distinct cellular compartments and processes. During sperm development in a number of diferent organisms, MYO6 carries out pivotal functions. In Drosophila, the MYO6 ortholog regulates actin reorganization during spermatid individualization and male KO fies are sterile. In C. elegans, the MYO6 ortholog mediates asymmetric segregation of cytosolic material and spermatid budding through cytokinesis, whereas in mice, this myosin regu- lates assembly of highly specialized actin-rich structures and formation of membrane compartments to allow the formation of fully diferentiated sperm. In this review, we will present an overview and compare the diverse function of MYO6 in the specialized adaptations of spermiogenesis in fies, worms, and mammals. Keywords Actin · C. elegans · Drosophila · Mouse · Myosin VI · Spermiogenesis Introduction and the maturation phase (Toshimori 2009); (Fig. 1). During the Golgi phase, proacrosomal vesicles (Fig. 1, 1) derived Sequential stages of mammalian spermiogenesis from the trans-Golgi network and the endocytic pathway fuse to form the acrosomal vesicle (Fig. 1, 2), which contains Spermiogenesis is the fnal stage of spermatogenesis, an the acrosomal granule (Fig. 1, 3). The acrosomal vesicle evolutionally conserved diferentiation process that results adheres through a cytoskeletal plate called the acroplax- in the formation of mature spermatozoa. In mammals, sper- ome (Fig. 1, 4) to the nuclear envelope. As demonstrated miogenesis can be divided through microscopic observations in rodents, the acroplaxome consists of actin flaments and into four distinct phases: the Golgi, the cap, the acrosome, the intermediate flament protein, SAK57 (spermatogenic cell/sperm-associated keratin of molecular mass 57 kDa), which forms the marginal ring terminating the acroplaxome * Folma Buss and connecting, together with additional linker proteins, the [email protected] acrosome to the nuclear lamina (Kierszenbaum et al. 2003a). During the cap phase, the acrosomal vesicle fattens out and 1 Department of Cellular and Molecular Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus spreads over the spermatid nucleus to form a cap (Fig. 1, University in Toruń, Torun, Poland 5); (Toshimori 2009). This process of acrosomal reshaping 2 Centre for Modern Interdisciplinary Technologies, Nicolaus and spermatid elongation is mediated by the fexible F-actin Copernicus University in Toruń, Torun, Poland scafold of the acroplaxome (Fig. 1, 6); (Kierszenbaum et al. 3 Cambridge Institute for Medical Research, The Keith 2003a, 2011). During the acrosomal phase, another tran- Peters Building, University of Cambridge, Hills Road, sient structure, the manchette, is formed (Fig. 1, 7), which Cambridge CB2 0XY, UK Vol.:(0123456789)1 3 324 Histochemistry and Cell Biology (2021) 155:323–340 Fig. 1 Schematic diagram highlighting the sequential steps of mouse ticipates in the formation of the sperm fagellum. At this stage, sper- spermiogenesis. During the Golgi phase, proacrosomal vesicles (1) matids are attached to Sertoli cells through the apical ES (8) which fuse to form the acrosomal vesicle (2), which contains the acroso- also supports their movement across the seminiferous tubule. Finally, mal granule (3). The acrosomal vesicle adheres to the nuclear enve- during the maturation phase, the elongation of the spermatid is com- lope through the acroplaxome (4). During the cap phase, the acroso- pleted and most of the cytoplasm and organelles are removed and mal vesicle fattens and spreads over the nucleus to form a cap (5). phagocytosed by Sertoli cells. The TBCs form at the spermatid-Ser- Acrosomal reshaping and spermatid elongation is mediated by the toli cell interface (9) and internalize cell–cell junctions supporting the acroplaxome (6). During the acrosomal phase, the manchette (7) par- sperm release. Sc Sertoli cell, SpT spermatid consists of a perinuclear ring, and contains actin flaments ends with sperm release to the lumen of seminiferous tubules and microtubules that extend into the elongating sperm tail in a process called spermation. The still non-motile sperm (Kierszenbaum et al. 2002, 2003a, 2007). The manchette is is transported to the epididymis, where the major part of involved in sperm head shaping and protein transport along the maturation process occurs, before the fnal capacitation the cytoskeleton important for formation of the sperm fa- to acquire hypermotility that takes place within the female gellum. Finally, the elongation of spermatids is completed reproductive tract (Skerget et al. 2015). Moreover, some of during the maturation phase, and most of the spermatid cyto- the luminal components of the epididymis, which are crucial plasm and organelles are discarded in the form of residual for fnal sperm maturation, such as the androgen binding bodies that are phagocytosed by Sertoli cells. Two additional protein, transferrin, and immobilin, are also endocytosed and testis-specifc structures are formed during spermiogenesis recycled by the microvillar epididymal epithelium (Zhou in mammals—the apical ectoplasmic specialization (apical et al. 2018). ES); (Fig. 1, 8) and the tubulobulbar complexes (TBCs); (Fig. 1, 9). The apical ES is a specialized actin-rich structure Actin cytoskeleton in spermiogenesis formed between spermatids and Sertoli cells and is com- posed of parallel actin bundles sandwiched between the sper- Directly after meiosis, haploid spermatids enter spermio- matid plasma membrane and the Sertoli cell’s endoplasmic genesis as round unpolarized cells that undergo excessive reticulum (ER); (Toyama 1976; Russell 1977; Franke et al. remodeling leading to the formation of mature sperm. In 1978; Sun et al. 2011). The apical ES anchors developing mammals, the actin cytoskeleton plays an undisputed role at spermatids to the Sertoli cells, positions the spermatid head several key points during this process serving as a cytoskel- regions in the correct orientation, and supports the spermatid etal track to guide exocytic vesicles from the Golgi to the movement across the seminiferous tubule. TBCs are also acrosome or from the manchette to the centrosome/axoneme. assembled at the spermatid–Sertoli cell interface and are In addition, actin flaments are crucial for the assembly involved in the internalization of cell–cell junctions to facili- and remodeling of testis-specifc structures important for tate sperm release (Upadhyay et al. 2012; Vogl et al. 2013). spermatid development, including the acrosome–acroplax- TBCs consist of a long endocytic proximal tubule stabilized ome–manchette complex, the apical ES, and the TBCs (Lie and cufed by a dense actin meshwork, an actin-free swollen et al. 2010b; O’Donnell et al. 2011; Upadhyay et al. 2012; bulbular region surrounded by endoplasmic reticulum, and a Qian et al. 2014a, b; Dunleavy et al. 2019; Pleuger et al., short distal tubule terminating in a clathrin-coated pit (Rus- 2020; Yang and Yang 2020). Actin dynamics is spatiotem- sell and Clermont, 1976; Russell 1979; Vogl et al. 1985). porally regulated by diferent actin-binding proteins (ABPs) After the reorganization of the apical ES and internaliza- and some of these actin regulators have been shown to be tion of cellular attachments via the TBCs, spermatogenesis involved in mammalian spermiogenesis. Localization data in 1 3 Histochemistry and Cell Biology (2021) 155:323–340 325 rat testes are available for a number of ABPs, such as espin, and precise spatiotemporal targeting. In addition, MYO6 has fmbrin, vinculin, plastin-3, and EPS8 (epidermal growth two unique inserts: the frst one in the motor domain near factor receptor pathway substrate 8), that are present at the the ATP-binding pocket may regulate ATPase activity, while apical ES (Grove and Vogl 1989; Grove et al. 1990; Bartles the second insert, also called the “reverse gear”, between et al. 1996; Chen et al. 1999; Lie et al. 2009; Siu et al. 2011; the motor domain and the lever arm is responsible for the Li et al. 2015) whereas the highly branched actin flament reverse reposition of the lever arm at the end of the power network of TBCs has been shown to associate with difer- stroke allowing its “backward” movement (Menetrey et al. ent
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