Afaf, a novel vesicle membrane protein, is related to acrosome formation in murine testis

Li, Yin-Chuan; Hu, Xinning; Zhang, Keying; Guo, Jian; Hu, Zheng-Da; Tao, Shixin; Xiao, Lijuan; Wang, Qingzhong; Han, Chunsheng; Liu, Yi‐Xun

doi:10.1016/j.febslet.2006.06.010

Cited by 40 publications

(42 citation statements)

References 19 publications

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“…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]. This evidence strongly supports the notion that the acrosome is a novel LRO.…”

Section: Discussionsupporting

confidence: 64%

“…Mouse anti-GFP monoclonal antibody (M20004) was purchased from Abmart (China). Afaf was made as previously described [14]. Goat anti-rabbit FITC, goat anti-mouse FITC, goat anti-rabbit TRITC, and goat anti-mouse TRITC-conjugated secondary antibodies as well as horseradish peroxidase (HRP)-conjugated secondary antibodies were purchased from Zhong Shan Jin Qiao (China).…”

Section: Antibodiesmentioning

confidence: 99%

“…To examine how Atg7 knockout affects acrosome biogenesis, the acrosome at different stages of spermiogenesis was labeled with an antibody against the acrosome membrane protein Afaf [14]. As shown in Figure 3A, proacrosomal vesicles derived from the Golgi apparatus were fused into a single acrosomal vesicle attached to one end of the nucleus in the Golgi-phase spermatids of Atg7 Flox/Flox mice.…”

Section: Abnormal Acrosome Biogenesis In Tnap-atg7 −/− Micementioning

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: Discussionsupporting

confidence: 64%

Section: Antibodiesmentioning

confidence: 99%

Section: Abnormal Acrosome Biogenesis In Tnap-atg7 −/− Micementioning

confidence: 99%

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Atg7 is required for acrosome biogenesis during spermatogenesis in mice

et al. 2014

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“…Other proteins resident at the acrosome follow an extra-Golgi pathway. The list includes MN9/equatorin/AFAF (Toshimori et al 1992, Li et al 2006, SPE-39 (Zhu et al 2009) and SMAP2 (Funaki et al 2013), i.e., proteins that in somatic cells localize to early endosomes and/ or function in early endosome-to-TGN transport. Hence, the acrosome could be effectively thought as an LRO, i.e., a peculiar membranous organelle indispensable for carrying on a cell type-specific physiological function.…”

Section: Discussionmentioning

confidence: 99%

“…During the AR, not all the acrosomal proteins are lost; some proteins such as IZUMO and equatorin , known also as MN9 antigen (Toshimori et al 1992) and/or AFAF (Li et al 2006), change their localization. The relocation of equatorin and IZUMO from the acrosome to the cell surface is thought to be important for priming sperm molecules for sperm-egg interaction and fusion respectively.…”

Section: Usp8/ubpy Met and The Acrosome Reactionmentioning

confidence: 99%

USP8/UBPy-regulated sorting and the development of sperm acrosome: the recruitment of MET

Berruti

Paiardi

2015

Reproduction

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The acrosome is a peculiar vacuole that at fertilization undergoes the acrosome reaction (AR), an event unique in the sperm life. Contents released promote sperm penetration through oocyte's investments; membranous components are involved in sperm-egg interaction/fusion. Therefore, both constituents play a role in fertilization. The biogenesis of this vacuole, however, has not been clarified yet; recently, it has been proposed as a novel lysosome-related organelle (LRO). Our research focuses on the involvement of the endosomal pathway in acrosomogenesis starting from the early phases. The trafficking sorted by USP8/UBPy, an endosomal regulator recently described as a compelling candidate for male fertility gene, was investigated in comparison to that of SP56, a marker of the biosynthetic pathway. Mouse spermatids were double/triple immunolabeled and examined by confocal microscopy. The contribution of the vesicular traffic assisted by the cortical microtubule array was also evaluated in nocodazole-treated spermatids. USP8/UBPy-sorted cargo contributes early to acrosomogenesis and its trafficking is microtubule mediated. It was identified, through co-immunoprecipitation/co-immunolocalization assays, that the membrane receptor MET, described herein for the first time in spermatids, as an USP8/UBPy-target substrate is delivered to the acrosome. MET and USP8/UBPy still colocalize in epididymal spermatozoa. Following the AR, MET and USP8/UBPy show a distinct fate. MET, in particular, translocates at the PAS, the post acrosomal segment known to harbor sperm-borne factors involved in oocyte activation. Overall, our results support the concept of the acrosome as a LRO and provide evidence for the identification of MET as a tyrosine kinase receptor that may play a role in fertilization.

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Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 2: Changes in spermatid organelles associated with development of spermatozoa

Hermo

Pelletier

Cyr

et al. 2009

Microscopy Res & Technique

103

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Spermiogenesis is a long process whereby haploid spermatids derived from the meiotic divisions of spermatocytes undergo metamorphosis into spermatozoa. It is subdivided into distinct steps with 19 being identified in rats, 16 in mouse and 8 in humans. Spermiogenesis extends over 22.7 days in rats and 21.6 days in humans. In this part, we review several key events that take place during the development of spermatids from a structural and functional point of view. During early spermiogenesis, the Golgi apparatus forms the acrosome, a lysosome-like membrane bound organelle involved in fertilization. The endoplasmic reticulum undergoes several topographical and structural modifications including the formation of the radial body and annulate lamellae. The chromatoid body is fully developed and undergoes structural and functional modifications at this time. It is suspected to be involved in RNA storing and processing. The shape of the spermatid head undergoes extensive structural changes that are species-specific, and the nuclear chromatin becomes compacted to accommodate the stream-lined appearance of the sperm head. Microtubules become organized to form a curtain or manchette that associates with spermatids at specific steps of their development. It is involved in maintenance of the sperm head shape and trafficking of proteins in the spermatid cytoplasm. During spermiogenesis, many genes/proteins have been implicated in the diverse dynamic events occurring at this time of development of germ cells and the absence of some of these have been shown to result in subfertility or infertility.

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Afaf, a novel vesicle membrane protein, is related to acrosome formation in murine testis

Cited by 40 publications

References 19 publications

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

USP8/UBPy-regulated sorting and the development of sperm acrosome: the recruitment of MET

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 2: Changes in spermatid organelles associated with development of spermatozoa

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