LINCking the Nuclear Envelope to Sperm Architecture

Manfrevola, Francesco; Guillou, Florian; Fasano, Silvia; Pierantoni, Riccardo; Chianese, Rosanna

doi:10.3390/genes12050658

Cited by 14 publications

(21 citation statements)

References 149 publications

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“…Thus, it is more likely that DNALI1 associates with the manchette microtubules through dynein heavy chain 1. Another function of the manchette is to help shape the head of developing spermatids (47, 48). Like the Meig1 and Pacrg mutant mice, the Dnali1 cKO mice also developed abnormal sperm heads, which further supports the claim that DNALI1 is involved in the construction of a functional manchette.…”

Section: Discussionmentioning

confidence: 99%

MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis

Yap

Huang

et al. 2022

Preprint

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Axonemal dynein light intermediate polypeptide 1 (DNALI1) was originally cloned from Chlamydomonas reinhardtii in an effort to find motor proteins essential for flagellar motility. Here we report that DNALI1 is a binding partner of parkin co-regulated gene 1 (PACRG), which forms a complex with meiosis expressed gene 1 (MEIG1) in the manchette, a transient and unique structure only present in the elongating spermatids and required for normal spermiogenesis of the male germ cell differentiation process. DNALI1 recruits the PACRG protein in transfected CHO cells, and also stabilizes PACRG in bacteria and transfected mammalian cells. The untagged DNALI1 could also be co-purified with His-tagged PACRG in the gel filtration assay. Immunofluorescence staining on isolated male germ cells revealed that DNALI1 was present in the manchette of elongating spermatids, and colocalized with PACRG in this structure. In Pacrg mutant mice, localization of DNALI1 in the manchette was not changed, suggesting that DNALI1 and PACRG form a complex in the manchette, with DNALI1 being an upstream molecule. Mice deficiency in DNALI1 specifically in male germ cells showed dramatically reduced sperm numbers and were infertile. In addition, majority of the sperm exhibited abnormal morphology including misshapen heads, bent tails and enlarged midpiece, discontinuous accessory structure, and loss of sperm individualization, emphasizing the importance of DNALI1 in sperm development. Examination of testis histology revealed impaired spermiogenesis in the conditional Dnali1 knockout mice. Electron microscopy revealed disrupted ultrastructure in sperm of the Dnali1 mutant mice. Testicular levels of MEIG1, PACRG and SPAG16L proteins were not changed in the Dnali1 mutant mice. However, MEIG1 and SPAG16L were no longer present in the manchette in the absence of DNALI1. These findings demonstrate that DNALI1 is involved in the connection of the MEIG1/PACRG complex to carry cargo proteins along the manchette microtubules for sperm flagella formation. Given that Dnali1 mutant mice showed impaired sperm individualization that was not observed in the MEIG1 nor PACRG-deficient mice, DNALI1 might fulfill other functions beyond its role associated with the MEIG1/PACRG complex. Thus, DNALI1 plays multiple roles in sperm cell differentiation and function.Summary statementAxonemal dynein light intermediate polypeptide 1 (DNALI1) is required for sperm formation and male fertility. It associates with the MEIG1/PACRG complex in the manchette and is involved in a cargo transport system. In addition, it might be related to IFT and sperm individualization.

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Section: Discussionmentioning

confidence: 99%

MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis

Yap

Huang

et al. 2022

Preprint

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“…Important biological processes including cytoarchitecture organization, chromatin remodeling, and the optimal maintenance of male fertility are under the control of ANKRD proteins ( Cunhaa and Mohler, 2009 ; Argudo et al, 2019 ; Tang et al, 2020 ; Manfrevola et al, 2021a ). In this scenario, particular attention has been given to ANKRD31, a key regulator of male meiosis and epididymal sperm maturation ( Boekhout et al, 2019 ; Acquaviva et al, 2020 ; Manfrevola et al, 2021b ).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, mechanotransduction pathways, through the formation of cytoskeletal–nucleoskeletal connections, transduce extracellular mechanical forces into biochemical signals propagating them along the cytoskeleton to the nuclear envelope, in order to regulate chromatin organization and gene expression, as the final biological effect ( Uhler and Shivashankar, 2017 ; Manfrevola et al, 2021a ). New insights regarding the involvement of ANKRDs in mechanotransduction have been reported as ANKRDs, interacting with mechanosensitive channels, are required for the cytoplasmic transmission of mechanosensory activity in neurons ( Argudo et al, 2019 ; Tang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

KISS1R and ANKRD31 Cooperate to Enhance Leydig Cell Gene Expression via the Cytoskeletal-Nucleoskeletal Pathway

Ricci

Guillou

Catizone

et al. 2022

Front. Cell Dev. Biol.

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Kisspeptins are involved in the regulation of hypothalamic-pituitary-gonadal axis, Leydig cell functions, and testosterone secretion, acting as endogenous ligands of the KISS1 receptor. ANKRD31 protein participates in male fertility, regulating meiotic progression, and epididymal sperm maturation. Here, we show that in Leydig cells, KISS1 receptor and ANKRD31 proteins physically interact; the formation of this protein complex is enhanced by Kisspeptin-10 that also modulates F-actin synthesis, favoring histone acetylation in chromatin and gene expression via the cytoskeletal–nucleoskeletal pathway. Kp/KISS1R system deregulation, expression impairment of cytoskeletal–nucleoskeletal mediators, Leydig gene targets, and the decreased testosterone secretion in Ankrd31−/− testis strongly supported our hypothesis. Furthermore, cytochalasin D treatment subverted the gene expression induction dependent on Kisspeptin-10 action. In conclusion, the current work highlights a novel role for the Kisspeptin-10 in the induction of the cytoskeletal–nucleoskeletal route, downstream a physical interaction between KISS1 receptor and ANKRD31, with gene expression activation as final effect, in Leydig cells.

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“…Bridging the nuclear envelope to link the nucleoskeleton to the cytoskeleton is achieved by the binding to KASH-domain proteins that interact with their N-terminal ends with the cytoskeleton. Although currently no specific KASH-domain proteins have been identified that are involved in HTCA formation, SUN5 interacts with the KASH-domain protein nesprin3 in spermatozoa, indicating that the HTCA comprises at least the SUN5/nesprin3 LINC complex [ 167 , 201 , 202 ].…”

Section: The Protein Components Of the Connecting Piece And Their Relevance For The Head-to-tail Linkage And Male Fertilitymentioning

confidence: 99%

The Transformation of the Centrosome into the Basal Body: Similarities and Dissimilarities between Somatic and Male Germ Cells and Their Relevance for Male Fertility

Contreras¹,

Hoyer‐Fender²

2021

Cells

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The sperm flagellum is essential for the transport of the genetic material toward the oocyte and thus the transmission of the genetic information to the next generation. During the haploid phase of spermatogenesis, i.e., spermiogenesis, a morphological and molecular restructuring of the male germ cell, the round spermatid, takes place that includes the silencing and compaction of the nucleus, the formation of the acrosomal vesicle from the Golgi apparatus, the formation of the sperm tail, and, finally, the shedding of excessive cytoplasm. Sperm tail formation starts in the round spermatid stage when the pair of centrioles moves toward the posterior pole of the nucleus. The sperm tail, eventually, becomes located opposed to the acrosomal vesicle, which develops at the anterior pole of the nucleus. The centriole pair tightly attaches to the nucleus, forming a nuclear membrane indentation. An articular structure is formed around the centriole pair known as the connecting piece, situated in the neck region and linking the sperm head to the tail, also named the head-to-tail coupling apparatus or, in short, HTCA. Finally, the sperm tail grows out from the distal centriole that is now transformed into the basal body of the flagellum. However, a centriole pair is found in nearly all cells of the body. In somatic cells, it accumulates a large mass of proteins, the pericentriolar material (PCM), that together constitute the centrosome, which is the main microtubule-organizing center of the cell, essential not only for the structuring of the cytoskeleton and the overall cellular organization but also for mitotic spindle formation and chromosome segregation. However, in post-mitotic (G1 or G0) cells, the centrosome is transformed into the basal body. In this case, one of the centrioles, which is always the oldest or mother centriole, grows the axoneme of a cilium. Most cells of the body carry a single cilium known as the primary cilium that serves as an antenna sensing the cell’s environment. Besides, specialized cells develop multiple motile cilia differing in substructure from the immotile primary cilia that are essential in moving fluids or cargos over the cellular surface. Impairment of cilia formation causes numerous severe syndromes that are collectively subsumed as ciliopathies. This comparative overview serves to illustrate the molecular mechanisms of basal body formation, their similarities, and dissimilarities, in somatic versus male germ cells, by discussing the involved proteins/genes and their expression, localization, and function. The review, thus, aimed to provide a deeper knowledge of the molecular players that is essential for the expansion of clinical diagnostics and treatment of male fertility disorders.

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LINCking the Nuclear Envelope to Sperm Architecture

Cited by 14 publications

References 149 publications

MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis

MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis

KISS1R and ANKRD31 Cooperate to Enhance Leydig Cell Gene Expression via the Cytoskeletal-Nucleoskeletal Pathway

The Transformation of the Centrosome into the Basal Body: Similarities and Dissimilarities between Somatic and Male Germ Cells and Their Relevance for Male Fertility

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