The Acrosome--Lysosome Relationship

Hartree, E. F.

doi:10.1530/jrf.0.0440125

Cited by 37 publications

(19 citation statements)

References 11 publications

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“…The mammalian acrosome contains many enzymes associated with lysosomes in somatic cells, and both acrosomes and lysosomes share a common feature, which is their low internal acidic pH [22]. According to these similarities, the acrosome has been postulated to be a modified lysosome [4]. Components of the endocytic machinery, such as Afaf [14], SH3P13 [23], SPE-39 [24], UBPy [25], RasGRF1 [26], and Vps54 [27,28], are involved in the biogenesis of the acrosome [2].…”

Section: Discussionmentioning

confidence: 99%

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Atg7 is required for acrosome biogenesis during spermatogenesis in mice

et al. 2014

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The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The molecular mechanism underlying the biogenesis of this lysosome-related organelle (LRO) is still largely unknown. Here, we show that germ cell-specific Atg7-knockout mice were infertile due to a defect in acrosome biogenesis and displayed a phenotype similar to human globozoospermia; this reproductive defect was successfully rescued by intracytoplasmic sperm injections. Furthermore, the depletion of Atg7 in germ cells did not affect the early stages of development of germ cells, but at later stages of spermatogenesis, the proacrosomal vesicles failed to fuse into a single acrosomal vesicle during the Golgi phase, which finally resulted in irregular or nearly round-headed spermatozoa. Autophagic flux was disrupted in Atg7-depleted germ cells, finally leading to the failure of LC3 conjugation to Golgi apparatus-derived vesicles. In addition, Atg7 partially regulated another globozoospermia-related protein, Golgi-associated PDZ-and coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally, the injection of either autophagy or lysosome inhibitors into testis resulted in a similar phenotype to that of germ cell-specific Atg7-knockout mice. Altogether, our results uncover a new role for Atg7 in the biogenesis of the acrosome, and we provide evidence to support the autolysosome origination hypothesis for the acrosome.

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Section: Discussionmentioning

confidence: 99%

“…The acrosome is regarded as a modified lysosome [4] or a novel lysosome-related organelle (LRO) [2,3]. However, the lysosome in mammalian cells is smaller than the acrosome.…”

Section: Introductionmentioning

confidence: 99%

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

et al. 2014

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“…For example, mannose-6-phosphate residues on glycoproteins are important in targeting these proteins to lysosomes. It has been suggested that acrosome biogenesis is functionally related to the formation of secretory lysosomes (Hartree 1975, Moreno & Alvarado 2006. The acrosome contains several enzymes that are also found in lysosomes (e.g.…”

Section: Discussionmentioning

confidence: 99%

Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice

Doran

Walters²,

Kyle³

et al. 2016

Reproduction

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The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for β-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis. Reproduction (2016) 152 91-99 IntroductionSpermatogenesis is the developmental process by which spermatozoa are produced from spermatogonial germ cells in the gonads (Grootegoed et al. 1995, Jan et al. 2012. At the start of this process, spermatogonial cells give rise to primary spermatocytes, which progress through meiosis to produce haploid spermatids. The spermatids subsequently undergo spermiogenesis, a complex series of morphological changes to form spermatozoa (Toshimori & Ito 2003). During spermiogenesis, chromatin condensation and nuclear remodelling occur, and also formation of the acrosome that contains glycosylated enzymes essential for egg fertilization. The acrosome is formed by the fusion of proacrosomal vesicles derived from the Golgi apparatus, which fuse to form a cap structure over the nucleus. A flagellum with the central 9 + 2 microtubular axoneme is also formed during spermiogenesis and contains a mid-piece packed with mitochondria to provide energy for motility.Defects in spermiogenesis contribute to male infertility problems in humans. Globozoospermia is one such syndrome that is found in around 0.1% of infertile men (Dam et al. 2007a). The disorder is characterized by round-headed sperm with a disrupted acrosome and abnormal mitochondrial localization. Genes that cause globozoospermia have been identified in mutant mice, www.reproduction-online.org transmembrane domains and a region similar to the facilitative glucose transporter specific P-E-S-P-R motif at the end of the 6th transmembrane domain. These characte ristics suggest that the Mfsd14a gene may encode a novel sugar transporter, but the solute specificity of the protein is not known.To establish the physiological function of the MFSD14A protein in vivo, we generated a transgenic mouse line with a LacZ gene insertion that disrupts the expression of the Mfsd14a gene. Phenotypic charac...

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“…It was initially thought to be a modified lysosome [37], but subsequent studies established that the acrosome is a Golgi-derived secretory vesicle [38], [39]. The acrosome forms during the beginning of spermiogenesis [4].…”

Section: Discussionmentioning

confidence: 99%

Mouse RC/BTB2, a Member of the RCC1 Superfamily, Localizes to Spermatid Acrosomal Vesicles

et al. 2012

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Mouse RC/BTB2 is an unstudied protein of the RCC1 (Regulator of Chromosome Condensation) superfamily. Because of the significant remodeling of chromatin that occurs during spermiogenesis, we characterized the expression and localization of mouse RC/BTB2 in the testis and male germ cells. The Rc/btb2 gene yields two major transcripts: 2.3 kb Rc/btb2-s, present in most somatic tissues examined; and 2.5 kb Rc/btb2-t, which contains a unique non-translated exon in its 5′-UTR that is only detected in the testis. During the first wave of spermatogenesis, Rc/btb2-t mRNA is expressed from day 8 after birth, reaching highest levels of expression at day 30 after birth. The full-length protein contains three RCC1 domains in the N-terminus, and a BTB domain in the C-terminus. In the testis, the protein is detectable from day 12, but is progressively up-regulated to day 30 and day 42 after birth. In spermatids, some of the protein co-localizes with acrosomal markers sp56 and peanut lectin, indicating that it is an acrosomal protein. A GFP-tagged RCC1 domain is present throughout the cytoplasm of transfected CHO cells. However, both GFP-tagged, full-length RC/BTB2 and a GFP-tagged BTB domain localize to vesicles in close proximity to the nuclear membrane, suggesting that the BTB domain might play a role in mediating full-length RC/BTB2 localization. Since RCC1 domains associate with Ran, a small GTPase that regulates molecular trafficking, it is possible that RC/BTB2 plays a role in transporting proteins during acrosome formation.

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The Acrosome--Lysosome Relationship

Cited by 37 publications

References 11 publications

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice

Mouse RC/BTB2, a Member of the RCC1 Superfamily, Localizes to Spermatid Acrosomal Vesicles

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