Furthermore, this study suggests an involvement of LAP1 in manchette development and chromatin regulation possibly via conversation with acetylated -tubulin and lamins, respectively

Furthermore, this study suggests an involvement of LAP1 in manchette development and chromatin regulation possibly via conversation with acetylated -tubulin and lamins, respectively. in spermatids, LAP1 can contribute to the achievement of non-random, sperm-specific chromatin distribution, as well as modulate cellular remodeling during spermiogenesis. In addition, LAP1 seems to be associated with dynamic microtubule changes related to manchette formation and flagella development. gene, that binds directly to lamins and indirectly to chromosomes [13,14]. However, despite being one of the first LAPs recognized [13], the physiological functions of this ubiquitously-expressed NE protein remain poorly comprehended. Nevertheless, LAP1 has been implicated in the regulation of the NE structure, cell cycle progression, mitosis, NE localization of torsinA and regulation of its ATPase activity, as well as skeletal muscle mass maintenance [14,15,16]. In Mctp1 our previous work, LAP1 was found in the mitotic spindle, mid-body and centrosomes, indicating a strong functional association between LAP1 and these cell cycle-related components. Specifically, LAP1 colocalizes with -tubulin in centrosomes at metaphase and anaphase during mitosis. In addition, LAP1 depletion seems to be correlated with altered centrosome positioning and a decrease in the number of mitotic cells [15]. LAP1 association with cell cycle progression is particularly interesting as it shares functional elements with spermatogenesis, in particular with meiosis. Through the study of LAP1 interacting proteins, it was possible to extrapolate biological functions inherent to LAP1 itself [17]. For instance, an important LAP1 interactor is the major eukaryotic protein phosphatase 1 (PP1) [18]. Regulation of PP1 cellular functions is determined by the formation of complexes with different PP1 interacting proteins (PIPs), and LAP1 has been identified as a novel PIP, specifically as a PP1-substrate [18,19]. In mammals, you will find four PP1 isoforms: PP1, PP1/ and the splice variants PP11 and PP12 [20]. PP12 is an important testis-specific and sperm-enriched isoform associated with spermatogenesis and sperm motility [21,22]. PP1 isoform expression profiles vary in mouse testis depending on the cell type, but its presence in human spermatogenesis has never been exhibited. In mouse, PP11 and PP1 expressions are restricted to spermatogonia, pachytene spermatocytes and somatic cells. Amazingly, PP12 is the only isoform present in secondary spermatocytes, round spermatids and elongating spermatids [23,24]. LAP1 also binds directly to Lamotrigine structural protein components of the NE, the nuclear lamins [14]. The composition and properties of the nuclear lamina in spermatogenic cells differ significantly from those of somatic cells in the same species [25,26]. For instance, the presence and Lamotrigine distribution of A-type lamins (lamins A and C) in mouse testis has been investigated, but the results are inconsistent. Overall, lamin A/C has been explained in Sertoli and Leydig cells [27], pachytene spermatocytes [28] and in the perinuclear region Lamotrigine of elongated spermatids [28,29]. Nonetheless, Shen and colleagues have shown that this decreased expression of lamin A/C caused a significant increase in sperm head abnormalities [29]. In addition, a rodent meiosis-specific A-type lamin, the isoform C2, was found to regulate chromosome dynamics and to promote efficient homologous recombination in mouse [30,31]. Conversely, B-type lamins are generally expressed during the whole mouse spermatogenic cycle [27,28], but lamin B1 in particular has never been investigated in mouse spermatogenesis. Lamin B3, a testis-specific isoform, is present in mouse spermiogenesis, concentrating at the posterior pole of elongating spermatids [32]. Nuclear lamin distribution in human spermatogenesis is still not obvious. Machiels and colleagues disclosed that, while both A- and B-type lamins were present in Sertoli, Leydig and peritubular cells, only B-type lamins were expressed in spermatogonia, and A-type lamins were solely observed in spermatocytes [33]. Alternatively, Elkhatib et al. confirmed the presence of A-type lamins only in somatic cells. In addition, this group exhibited that lamins B1, B2 and, probably, B3 are all expressed in the nuclear periphery of human spermatids, accumulating at the posterior pole during the maturation process [26]. Therefore, lamin B1 in particular Lamotrigine was only associated with human spermiogenesis. Overall, the cellular distribution of lamins A/C and B1 in the various stages of spermatogenesis is not fully.