The mammalian acrosome as a secretory lysosome: New and old evidence

Moreno, Ricardo D.; Alvarado, Carlos P

doi:10.1002/mrd.20581

Cited by 91 publications

(87 citation statements)

References 41 publications

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“…2) in keeping with the known activity of this enzyme in the immune system (Boulland et al 2007). The localization of this enzyme in the sperm acrosome is also consistent with the observation that this enzyme is maximally active at acidic pH and is preferentially targeted to lysosomes (Mason et al 2004); the acrosomal vesicle is known to exhibit a low intraacrosomal pH and shares many features with cellular lysosomes (Working & Meizel 1983, Moreno & Alvarado 2006. Importantly, the anti-IL4I1 antibody used in this study could not discriminate between the two isoforms of this molecule, because the translated protein generated by the two genes represented in Fig.…”

Section: Discussionsupporting

confidence: 77%

Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function

Houston¹,

Curry²,

Aitken³

2015

Reproduction

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Reactive oxygen species (ROS) are known to play an important role in the regulation of human sperm function. In this study, we demonstrate for the first time that human spermatozoa possess interleukin-induced gene 1 (IL4I1), an L-amino acid oxidase (LAAO) which is capable of generating ROS on exposure to aromatic amino acids in the presence of oxygen. The preferred substrates were found to be phenylalanine and tryptophan while the enzyme was located in the acrosomal region and midpiece of these cells. In contrast to equine and bovine spermatozoa, enzyme activity was lost as soon as the spermatozoa became non-viable. On a cell-to-cell basis human spermatozoa were also shown to generate lower levels of hydrogen peroxide than their equine counterparts on exposure to phenylalanine. Stimulation of LAAO activity resulted in the induction of several hallmarks of capacitation including tyrosine phosphorylation of the sperm flagellum and concomitant activation of phospho-SRC expression. In addition, stimulation of LAAO resulted in an increase in the levels of acrosomal exocytosis in both the presence and absence of progesterone stimulation, via mechanisms that could be significantly reversed by the presence of catalase. As is often the case with free radical-mediated phenomena, prolonged exposure of human spermatozoa to phenylalanine resulted in the stimulation of apoptosis as indicated by significant increases in mitochondrial superoxide generation and the activation of intracellular caspases. These results confirm the existence of an LAAO in human spermatozoa with a potential role in driving the redox regulation of sperm capacitation and acrosomal exocytosis.

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Section: Discussionsupporting

confidence: 77%

Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function

Houston¹,

Curry²,

Aitken³

2015

Reproduction

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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].…”

Section: Discussionmentioning

confidence: 99%

“…Beclin1 and LC3-A have been implicated in the maturation of a specialized LRO, the melanosome [43]. As a novel LRO, the acrosome is regarded as a secretory lysosome not only because of its internal acid pH but also because it contains many enzymes associated with lysosomes in somatic cells [22]. Upon fertilization, the acrosome reaction initiates, and the membrane surrounding the acrosome bursts and exposes the contents of the acrosome to remove cumulus cells or break down the outer membrane of the oocyte to fertilize it [44].…”

Section: Atg7 Is Involved In Acrosome Biogenesismentioning

confidence: 99%

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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“…Spermiogenesis is a unique process that involves the formation of the acrosome with a large vesicle structure, condensation of the nucleus, generation of the sperm tail and removal of most of the cytoplasm as a residual body. [27][28][29] Furthermore, bioinformatics analysis identified 84 proteins annotated to be involved in vesicle-related events, 22 proteins annotated to function in chromatin assembly, 39 proteins annotated to be involved in nucleocytoplasmic transport and 231 proteins having orthologues in human cilia. 30 The large-scale proteome that appears to be involved in unique processes during meiosis and spermiogenesis provides more detailed and accurate information to improve our understanding of the mechanisms that cause male infertility, such as in teratozoaspermia and asthenospermia, which are two major types of male infertility.…”

Section: Expressional Proteome Of the Testismentioning

confidence: 99%

Proteomics of spermatogenesis: from protein lists to understanding the regulation of male fertility and infertility

Huang¹,

Sha²

2010

Asian J Androl

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Proteomic technologies have undergone significant development in recent years, which has led to extensive advances in protein research. Currently, proteomic approaches have been applied to many scientific areas, including basic research, various disease and malignant tumour diagnostics, biomarker discovery and other therapeutic applications. In addition, proteomics-driven research articles examining reproductive biology and medicine are becoming increasingly common. The key challenge for this field is to move from lists of identified proteins to obtaining biological information regarding protein function. The present article reviews the available scientific literature related to spermatogenesis. In addition, this study uses two-dimensional electrophoresis mass spectrometry (2DE-MS) and liquid chromatography (LC)-MS to construct a series of proteome profiles describing spermatogenesis. This large-scale identification of proteins provides a rich resource for elucidating the mechanisms underlying male fertility and infertility.

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The mammalian acrosome as a secretory lysosome: New and old evidence

Cited by 91 publications

References 41 publications

Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function

Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

Proteomics of spermatogenesis: from protein lists to understanding the regulation of male fertility and infertility

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