Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

Abstract

Spermatogenesis comprises highly complex differentiation processes. Nuclear envelope (NE) proteins have been associated with these processes, including lamins, lamina-associated polypeptide (LAP) 2 and the lamin B-receptor. LAP1 is an important NE protein whose function has not been fully elucidated, but several binding partners allow predicting putative LAP1 functions. To date, LAP1 had not been associated with spermatogenesis. In this study, LAP1 expression and cellular/subcellular localization during spermatogenesis in human and mouse testes is established for the first time. The fact that LAP1 is expressed during nuclear elongation in spermiogenesis and is located at the spermatids’ centriolar pole is singularly important. LAP1 binds to members of the protein phosphatase 1 (PP1) family. Similar localization of LAP1 and PP1γ2, a testis-specific PP1 isoform, suggests a shared function for both proteins during spermiogenesis. Furthermore, this study suggests an involvement of LAP1 in manchette development and chromatin regulation possibly via interaction with acetylated α-tubulin and lamins, respectively. Taken together, the present results indicate that, by moving to the posterior pole 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.

Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility

“…) (Alsheimer et al ., ) and coincides in time with the chromosomal bouquet stage (Alsheimer & Benavente, ). Of note, the presence of A‐type lamins, together with lamin B1, has recently been demonstrated at the NE of human and mouse spermatocytes (Serrano et al ., ), which most likely reflects the expression of the meiosis‐specific C2 variant, given that somatic lamin A/C appears to be absent from mammalian spermatocytes, as discussed above. Interestingly, the distinctive subcellular localization of lamin C2 in discontinuous plaques is correlated with the lack of certain domains involved in the polymerization and stability of somatic lamins (Jahn et al ., ).…”

“…Lamin B1 is a ubiquitous protein present in most mammalian cells, whereas lamin A/C is mainly associated with terminal cellular differentiation. Among their many functions in somatic cells, these major lamin isoforms regulate chromatin organization and gene expression along with INM proteins by providing a platform for tethering chromatin to specific nuclear regions (Broers et al ., ), which has also been correlated with the process of spermatogenesis (Table ; see Section III.2) (Serrano et al ., ). In turn, while lamins A/C and B1 provide mechanical stiffness to somatic nuclei (Dobrzynska et al ., ), male germline cells specifically express lamins C2 and B3, shorter splice variants of somatic lamins C and B2, respectively.…”

“…The precise physiological role of LAP1 is not completely elucidated, although some functions have been suggested based on its association with several proteins at the NE in somatic cells, namely positioning of lamins and chromatin at the nuclear periphery, activation of torsinA ATPase activity, regulation of the localization of emerin:A‐type lamin complexes at the INM (Rebelo et al ., ), maintenance of NE structure and cell cycle progression (Santos et al ., ). Recently, a putative involvement of LAP1 in spermiogenesis‐specific nuclear remodelling has also been proposed (Table ; see Section III.2) (Serrano et al ., ).…”

“…LAP1 has been detected at the NE and, rather surprisingly, in a cytoplasmic dot juxtaposed to the nucleus of human spermatocytes before meiotic cell divisions (Table ) (Serrano et al ., ). A homogeneous distribution of LAP2 has also been found at the nuclear periphery of spermatocytes during prophase I in rats (Alsheimer et al ., , ) and mice (Table ) (Gob et al ., ).…”

“…() showed promising results for a possible role of lamin A/C in acrosome biogenesis (Table ). Additionally, the presence of A‐type lamins, presumably somatic lamin A/C, has recently been detected at the NE of human round spermatids and the acrosomal region of mouse elongated spermatids (Serrano et al ., ). Altogether, the biological relevance of lamin A/C during the post‐meiotic stages of mammalian spermatogenesis is far from being completely elucidated and deserves further investigation.…”