SPAG4L, a Novel Nuclear Envelope Protein Involved in the Meiotic Stage of Spermatogenesis

Jiang, Xianzhen; Yang, Ming-Gang; Huang, Lihua; Li, Chang-Qi; Xing, Xiaowei

doi:10.1089/dna.2010.1161

Cited by 34 publications

(27 citation statements)

References 22 publications

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“…The results presented above are clearly different from what was described in previous reports showing that Sun5 is mainly expressed during meiosis in the reticulum [12] and that Sun5 is located in the NE facing the acrosome and is not post-translationnally modified [11]. The main difference between our experiments and previous reports was the use of different antibodies.…”

Section: Discussioncontrasting

confidence: 99%

“…Contradictory results were published regarding Sun5 expression and localization. A first report has shown that Spag4l (alias of Sun5) and Spag4l-2 (a longer isoform of the same gene) are expressed after the meiosis and are located in the apical nuclear envelope of round spermatids facing the acrosome [11] whereas a second study reported an early and strong expression during meiosis [12]. Sun5 could therefore be one of the missing link between the nuclear envelope and the acroplaxome and may, with Dpy19l2, participate to the anchoring of the acroplaxome to the NE.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of Sun5 Localization during Spermatogenesis in Wild Type and Dpy19l2 Knock-Out Mice Indicates That Sun5 Is Not Involved in Acrosome Attachment to the Nuclear Envelope

et al. 2015

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The acrosome is an organelle that is central to sperm physiology and a defective acrosome biogenesis leads to globozoospermia, a severe male infertility. The identification of the actors involved in acrosome biogenesis is therefore particularly important to decipher the molecular pathogeny of globozoospermia. We recently showed that a defect in the DPY19L2 gene is present in more than 70% of globozoospermic men and demonstrated that Dpy19l2, located in the inner nuclear membrane, is the first protein involved in the attachment of the acrosome to the nuclear envelope (NE). SUN proteins serve to link the nuclear envelope to the cytoskeleton and are therefore good candidates to participate in acrosome-nucleus attachment, potentially by interacting with DPY19L2. In order to characterize new actors of acrosomal attachment, we focused on Sun5 (also called Spag4l), which is highly expressed in male germ cells, and investigated its localization during spermatogenesis. Using immunohistochemistry and Western blot experiments in mice, we showed that Sun5 transits through different cellular compartments during meiosis. In pachytene spermatocytes, it is located in a membranous compartment different to the reticulum. In round spermatids, it progresses to the Golgi and the NE before to be located to the tail/head junction in epididymal sperm. Interestingly, we demonstrate that Sun5 is not, as initially reported, facing the acrosome but is in fact excluded from this zone. Moreover, we show that in Dpy19l2 KO spermatids, upon the detachment of the acrosome, Sun5 relocalizes to the totality of the NE suggesting that the acrosome attachment excludes Sun5 from the NE facing the acrosome. Finally, Western-blot experiments demonstrate that Sun5 is glycosylated. Overall, our work, associated with other publications, strongly suggests that the attachment of the acrosome to the nucleus does not likely depend on the formation of SUN complexes.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamics of Sun5 Localization during Spermatogenesis in Wild Type and Dpy19l2 Knock-Out Mice Indicates That Sun5 Is Not Involved in Acrosome Attachment to the Nuclear Envelope

et al. 2015

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“…Male germ-line cells contain three other SUN proteins (Kracklauer et al, 2013), SUN3 (Göb et al, 2010), SUN4 (originally termed Spag4 (Shao et al, 1999;Tarnasky et al, 1998)) and SUN5 (also known as Spag4-like (Frohnert et al, 2011;Jiang et al, 2011)). Each of these conforms to the same general domain organization as SUN1/2 (Hasan et al, 2006;Liu et al, 2007).…”

Section: Mammalian Somatic Cells Contain Two Partially Redundant Sun mentioning

confidence: 99%

SUN4 is essential for nuclear remodeling during mammalian spermiogenesis

Calvi

Wong

Wright

et al. 2015

Developmental Biology

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One of the more dramatic examples of cellular reorganization occurs during spermiogenesis in which a roughly spherical spermatid is transformed into a mature sperm cell. A highlight of this process involves nuclear remodeling whereby the round spermatid nucleus is sculpted into an elongated and polar structure. This transformation in nuclear architecture features chromatin condensation, changes in the composition and organization of the nuclear lamina and redistribution and elimination of nuclear pore complexes. The manchette, a cytoplasmic microtubule-based structure is thought to play a crucial role in the remodeling process. Here we show that SUN4, a spermatid nuclear membrane protein has an essential function in coupling the manchette to the nuclear periphery. In the absence of SUN4, manchette microtubules appear highly disorganized and the nucleus itself fails to elongate. Consequently, mice deficient in SUN4 display globozoospermia with associated infertility.

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“…[5][6][7][8][9] LINC complexes and nuclear lamins form a solid scaffold for diverse functions including nuclear migration, 10 nuclear shaping and positioning,. 11,12 maintaining the centrosome-nucleus connection, 13,14 mechanotransduction, 15,16 DNA repair, 17,18 nuclear membrane spacing, cancer, and recessive cerebellar ataxia.…”

Section: Introductionmentioning

confidence: 99%

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration

Nishioka

Imaizumi

Imada

et al. 2016

Nucleus

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The LINC complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, such as nuclear migration, mechanotransduction and chromatin tethering in the meiotic phase. However, it remains unknown how these functions are regulated in different cell contexts. An inner nuclear membrane component of the LINC complex, SUN1, is ubiquitously expressed. The human SUN1 gene produces over 10 variants by alternative splicing. Although functions of SUN1 are relatively well characterized, functional differences among SUN1 splice variants are poorly characterized. LINC complex components are associated with a wide range of human diseases; therefore, it is important to understand the functional diversity among SUN1 splice variants. Here, we identified a novel human SUN1 splice variant, SUN1_888. overexpression of the SUN1 splice variants, SUN1_888 or SUN1_785, but not the predominant isoform, SUN1_916, activated directional cell migration. Knockdown of SUN1_888 suppressed cell migration; in contrast depletion of SUN1_916 activated cell migration. In addition, all of investigated SUN1 splicing variants rescued cell migration in SUN1 knock out cell. These results indicate that redundant and non-redundant functions of SUN1 splice variant in directional cell migration and suggest that variable LINC complexes with distinct task may exit. Furthermore, in contrast to previous studies, we showed association between SUN1 and B-type lamins. Interestingly, B-type lamin preferentially interacts with SUN1 but not SUN2. These results suggest that tissue-specific SUN1 variants variably interact with nucleoplasmic partners and allow variable assembly of LINC complexes that can be assigned to distinct tasks.

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SPAG4L, a Novel Nuclear Envelope Protein Involved in the Meiotic Stage of Spermatogenesis

Cited by 34 publications

References 22 publications

Dynamics of Sun5 Localization during Spermatogenesis in Wild Type and Dpy19l2 Knock-Out Mice Indicates That Sun5 Is Not Involved in Acrosome Attachment to the Nuclear Envelope

Dynamics of Sun5 Localization during Spermatogenesis in Wild Type and Dpy19l2 Knock-Out Mice Indicates That Sun5 Is Not Involved in Acrosome Attachment to the Nuclear Envelope

SUN4 is essential for nuclear remodeling during mammalian spermiogenesis

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration

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