TMF/ARA160 Governs the Dynamic Spatial Orientation of the Golgi Apparatus during Sperm Development

Elkis, Yoav; Bel, Shai; Rahimi, Roni; Lerer-Goldstein, Tali; Levin-Zaidman, Smadar; Babushkin, Tania; Shpungin, Sally; Nir, Uri

doi:10.1371/journal.pone.0145277

Cited by 20 publications

(14 citation statements)

References 59 publications

(90 reference statements)

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“…The male sterility phenotype in TMF knockout mice arises from defective acrosome biogenesis. The Golgi is mis-positioned in developing spermatids upon loss of TMF, and there is reduced tethering of pro-acrosomal vesicles, explaining the lack of a functional acrosome in these cells (Lerer-Goldshtein et al, 2010; Elkis et al, 2015). The results are consistent with a role for TMF in membrane delivery into the forming newly forming acrosome during spermatogenesis.…”

Section: Animal Models For Golgin Functionmentioning

confidence: 99%

The Physiological Functions of the Golgin Vesicle Tethering Proteins

Lowe

2019

Front. Cell Dev. Biol.

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The golgins comprise a family of vesicle tethering proteins that act in a selective manner to tether transport vesicles at the Golgi apparatus. Tethering is followed by membrane fusion to complete the delivery of vesicle-bound cargo to the Golgi. Different golgins are localized to different regions of the Golgi, and their ability to selectively tether transport vesicles is important for the specificity of vesicle traffic in the secretory pathway. In recent years, our mechanistic understanding of golgin-mediated tethering has greatly improved. We are also beginning to appreciate how the loss of golgin function can impact upon physiological processes through the use of animal models and the study of human disease. These approaches have revealed that loss of a golgin causes tissue-restricted phenotypes, which can vary in severity and the cell types affected. In many cases, it is possible to attribute these phenotypes to a defect in vesicular traffic, although why certain tissues are sensitive to loss of a particular golgin is still, in most cases, unclear. Here, I will summarize recent progress in our understanding of golgins, focusing on the physiological roles of these proteins, as determined from animal models and the study of disease in humans. I will describe what these in vivo analyses have taught us, as well as highlight less understood aspects, and areas for future investigations.

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Section: Animal Models For Golgin Functionmentioning

confidence: 99%

The Physiological Functions of the Golgin Vesicle Tethering Proteins

Lowe

2019

Front. Cell Dev. Biol.

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“…One of the earliest events during spermiogenesis is acrosome formation, an apical nuclear cap rich in hydrolytic enzymes, which is required for sperm penetration of the oocyte at fertilization. Biogenesis of the acrosome begins with trafficking of proacrosomal vesicles toward the spermatid nucleus from both the trans -Golgi network and the endocytic pathway [ 2 ]. These vesicles adhere to and fuse to form the acrosomal vesicle along the acroplaxome, a cytoskeletal actin-rich plate that anchors the developing acrosome to the nuclear envelope [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Loss of myosin VI expression affects acrosome/acroplaxome complex morphology during mouse spermiogenesis†

Zakrzewski

Rędowicz

Buß

et al. 2020

Biology of Reproduction

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During spermiogenesis in mammals, actin filaments and a variety of actin-binding proteins are involved in the formation and function of highly specialized testis-specific structures. Actin-based motor proteins, such as myosin Va and VIIa, play a key role in this complex process of spermatid transformation into mature sperm. We have previously demonstrated that myosin VI (MYO6) is also expressed in mouse testes. It is present in actin-rich structures important for spermatid development, including one of the earliest events in spermiogenesis—acrosome formation. Here, we demonstrate using immunofluorescence, cytochemical, and ultrastructural approaches that MYO6 is involved in maintaining the structural integrity of these specialized actin-rich structures during acrosome biogenesis in mouse. We show that MYO6 together with its binding partner TOM1/L2 is present at/around the spermatid Golgi complex and the nascent acrosome. Depletion of MYO6 in Snell’s waltzer mice causes structural disruptions of the Golgi complex and affects the acrosomal granule positioning within the developing acrosome. In summary, our results suggest that MYO6 plays an anchoring role during the acrosome biogenesis mainly by tethering of different cargo/membranes to highly specialized actin-related structures.

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“…Other transmembrane proteins in the Golgi such as TM9SF3, TMED4/p25, and TMED7/p27 have been reported to be involved in Golgi migration after acrosome formation [ 36 ]. In addition, KO of TMF/ARA160 (TATA Element Modulatory Factor 1), which localizes to the Golgi in mouse testis and associates with tubulin and microtubules, demonstrate spermiogenesis failure attributable to disorientation of the Golgi and abnormal trafficking of the Golgi-derived proacrosomal vesicles during early spermiogenic steps [ 37 ]. Thus, we believe that SSMEM1 functions to anchor Golgi and cytoskeletal proteins for proper Golgi migration analogous to TMF/ARA160.…”

Section: Discussionmentioning

confidence: 99%

Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male mice†

Nozawa

Zhang

Miyata

et al. 2020

Biology of Reproduction

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Globozoospermia (sperm with an abnormally round head shape) and asthenozoospermia (defective sperm motility) are known causes of male infertility in human patients. Despite many studies, the molecular details of the globozoospermia etiology are still poorly understood. Serine-rich single-pass membrane protein 1 (Ssmem1) is a conserved testis-specific gene in mammals. In this study, we generated Ssmem1 knockout (KO) mice using the CRISPR/Cas9 system, demonstrated that Ssmem1 is essential for male fertility in mice, and found that SSMEM1 protein is expressed during spermatogenesis but not in mature sperm. The sterility of the Ssmem1 KO (null) mice is associated with globozoospermia and loss of sperm motility. To decipher the mechanism causing the phenotype, we analyzed testes with transmission electron microscopy and discovered that Ssmem1-disrupted spermatids have abnormal localization of Golgi at steps eight and nine of spermatid development. Immunofluorescence analysis with anti-Golgin-97 to label the trans-Golgi network, also showed delayed movement of the Golgi to the spermatid posterior region, which causes failure of sperm head shaping, disorganization of the cell organelles, and entrapped tails in the cytoplasmic droplet. In summary, SSMEM1 is crucial for intracellular Golgi movement to ensure proper spatiotemporal formation of the sperm head that is required for fertilization. These studies and the pathway in which SSMEM1 functions have implications for human male infertility and identifying potential targets for nonhormonal contraception.

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TMF/ARA160 Governs the Dynamic Spatial Orientation of the Golgi Apparatus during Sperm Development

Cited by 20 publications

References 59 publications

The Physiological Functions of the Golgin Vesicle Tethering Proteins

The Physiological Functions of the Golgin Vesicle Tethering Proteins

Loss of myosin VI expression affects acrosome/acroplaxome complex morphology during mouse spermiogenesis†

Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male mice†

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