scholarly journals Cyclin–CDK Complexes are Key Controllers of Capacitation-Dependent Actin Dynamics in Mammalian Spermatozoa

2019 ◽  
Vol 20 (17) ◽  
pp. 4236 ◽  
Author(s):  
Bernabò ◽  
Ramal-Sanchez ◽  
Valbonetti ◽  
Machado-Simoes ◽  
Ordinelli ◽  
...  

Mammalian spermatozoa are infertile immediately after ejaculation and need to undergo a functional maturation process to acquire the competence to fertilize the female egg. During this process, called capacitation, the actin cytoskeleton dramatically changes its organization. First, actin fibers polymerize, forming a network over the anterior part of the sperm cells head, and then it rapidly depolymerizes and disappears during the exocytosis of the acrosome content (the acrosome reaction (AR)). Here, we developed a computational model representing the actin dynamics (AD) process on mature spermatozoa. In particular, we represented all the molecular events known to be involved in AD as a network of nodes linked by edges (the interactions). After the network enrichment, using an online resource (STRING), we carried out the statistical analysis on its topology, identifying the controllers of the system and validating them in an experiment of targeted versus random attack to the network. Interestingly, among them, we found that cyclin-dependent kinase (cyclin–CDK) complexes are acting as stronger controllers. This finding is of great interest since it suggests the key role that cyclin–CDK complexes could play in controlling AD during sperm capacitation, leading us to propose a new and interesting non-genomic role for these molecules.

2019 ◽  
Vol 31 (5) ◽  
pp. 1033
Author(s):  
Peng Zhang ◽  
Wanjun Jiang ◽  
Na Luo ◽  
Wenbing Zhu ◽  
Liqing Fan

The acrosome is single, large, dense-core secretory granule overlying the nucleus of most mammalian spermatozoa. Its exocytosis, the acrosome reaction, is a crucial event during fertilisation. In this study we identified a new acrosome-associated gene, namely IQ motif containing D (IQCD), expressed nearly in multiple tissues with highest expression levels in the testis. In mouse testis, Iqcd transcript accumulated from Postnatal Day (PND) 1 to adulthood. However, expression of IQCD protein at the testicular development stage started primarily from PND 18 and increased in an age-dependent manner until plateauing in adulthood. IQCD was primarily accumulated in the acrosome area of round and elongating spermatids within seminiferous tubules of the testes during the late stage of spermiogenesis; this immunolocalisation pattern is similar in mice and humans. IQCD levels in spermatozoa were significantly lower in IVF patients with total fertilisation failure or a low fertilisation rate than in healthy men. Anti-IQCD antibody significantly inhibited the acrosome reaction and slightly reduced protein tyrosine phosphorylation levels in human spermatozoa, but specifically blocked murine IVF. IQCD interacted with mammalian homolog of C. elegans uncoordinated gene 13 (Munc13) in spermatozoa and may participate in acrosome exocytosis. In conclusion, this study identified a new acrosomal protein, namely IQCD, which is involved in fertilisation and the acrosome reaction.


2017 ◽  
Vol 62 (No. 12) ◽  
pp. 519-526
Author(s):  
Y. Li ◽  
M. Sun ◽  
J. Zhu ◽  
G. Jiao ◽  
J. Lin ◽  
...  

Although it has been proposed that the Fas and Fas ligand (FasL) may protect ejaculated spermatozoa against apoptosis induced by lipoperoxidative damage and against lymphocytes present in the female genital tract, studies reported conflicting results on the presence of Fas receptors in ejaculated human spermatozoa. Furthermore, the expression of Fas/FasL on mature spermatozoa has not been observed in several important mammals. Using seven species, we observed the possibility for species difference in Fas/FasL expression on mature spermatozoa by both immunofluorescence microscopy and western blot analysis. Whereas intensive signals of Fas immunolabelling were detected in sperm head and middle piece and weak signals observed in the tail in 86–100% of the mouse, rat, bull, ram, and buck spermatozoa, only weak signals were detected on the whole body of 27% boar spermatozoa and in the head of 21% human spermatozoa. The pattern of FasL localization was identical to that of Fas in spermatozoa from human, mouse, rat, ram, and buck, but boar and bull spermatozoa showed weak and intensive FasL signals, respectively, only in the head. Western blotting further confirmed the Fas and FasL expression in mouse, rat, bull, ram, and buck, but not in human and boar spermatozoa. Taken together, the results revealed a marked species difference in Fas/FasL expression and an extensive co-expression of Fas and FasL among mature mammalian spermatozoa, suggesting that whereas spermatozoa from most species may be protected by Fas/FasL, those from human and boar may not use the Fas system for protection.


Author(s):  
Y. Lax ◽  
S. Grossman ◽  
S. Rubinstein ◽  
N. Magid ◽  
H. Breitbart

2007 ◽  
Vol 104 (18) ◽  
pp. 7688-7692 ◽  
Author(s):  
Betsy Navarro ◽  
Yuriy Kirichok ◽  
David E. Clapham

Mature mammalian spermatozoa are quiescent in the male reproductive tract. Upon ejaculation and during their transit through the female reproductive tract, they undergo changes that enable them to fertilize the egg. During this process of capacitation, they acquire progressive motility, develop hyperactivated motility, and are readied for the acrosome reaction. All of these processes are regulated by intracellular pH. In the female reproductive tract, the spermatozoan cytoplasm alkalinizes, which in turn activates a Ca2+-selective current (ICatSper) required for hyperactivated motility. Here, we show that alkalinization also has a dramatic effect on membrane potential, producing a rapid hyperpolarization. This hyperpolarization is primarily mediated by a weakly outwardly rectifying K+ current (IKSper) originating from the principal piece of the sperm flagellum. Alkalinization activates the pHi-sensitive IKSper, setting the membrane potential to negative potentials where Ca2+ entry via ICatSper is maximized. IKSper is one of two dominant ion currents of capacitated sperm cells.


1995 ◽  
Vol 130 (4) ◽  
pp. 919-927 ◽  
Author(s):  
B M Lange ◽  
K Gull

The centriole pair in animals shows duplication and structural maturation at specific cell cycle points. In G1, a cell has two centrioles. One of the centrioles is mature and was generated at least two cell cycles ago. The other centriole was produced in the previous cell cycle and is immature. Both centrioles then nucleate one procentriole each which subsequently elongate to full-length centrioles, usually in S or G2 phase. However, the point in the cell cycle at which maturation of the immature centriole occurs is open to question. Furthermore, the molecular events underlying this process are entirely unknown. Here, using monoclonal and polyclonal antibody approaches, we describe for the first time a molecular marker which localizes exclusively to one centriole of the centriolar pair and provides biochemical evidence that the two centrioles are different. Moreover, this 96-kD protein, which we name Cenexin (derived from the Latin, senex for "old man," and Cenexin for centriole) defines very precisely the mature centriole of a pair and is acquired by the immature centriole at the G2/M transition in prophase. Thus the acquisition of Cenexin marks the functional maturation of the centriole and may indicate a change in centriolar potential such as its ability to act as a basal body for axoneme development or as a congregating site for microtubule-organizing material.


2011 ◽  
Vol 366 (1584) ◽  
pp. 3572-3583 ◽  
Author(s):  
Frank Uhlmann ◽  
Céline Bouchoux ◽  
Sandra López-Avilés

The eukaryotic cell division cycle encompasses an ordered series of events. Chromosomal DNA is replicated during S phase of the cell cycle before being distributed to daughter cells in mitosis. Both S phase and mitosis in turn consist of an intricately ordered sequence of molecular events. How cell cycle ordering is achieved, to promote healthy cell proliferation and avert insults on genomic integrity, has been a theme of Paul Nurse's research. To explain a key aspect of cell cycle ordering, sequential S phase and mitosis, Stern & Nurse proposed ‘A quantitative model for cdc2 control of S phase and mitosis in fission yeast’. In this model, S phase and mitosis are ordered by their dependence on increasing levels of cyclin-dependent kinase (Cdk) activity. Alternative mechanisms for ordering have been proposed that rely on checkpoint controls or on sequential waves of cyclins with distinct substrate specificities. Here, we review these ideas in the light of experimental evidence that has meanwhile accumulated. Quantitative Cdk control emerges as the basis for cell cycle ordering, fine-tuned by cyclin specificity and checkpoints. We propose a molecular explanation for quantitative Cdk control, based on thresholds imposed by Cdk-counteracting phosphatases, and discuss its implications.


2011 ◽  
Vol 301 (4) ◽  
pp. C750-C761 ◽  
Author(s):  
Jean Defourny ◽  
François Lallemend ◽  
Brigitte Malgrange

In mammals, sensorineural deafness results from damage to the auditory receptors of the inner ear, the nerve pathways to the brain or the cortical area that receives sound information. In this review, we first focused on the cellular and molecular events taking part to spiral ganglion axon growth, extension to the organ of Corti, and refinement. In the second half, we considered the functional maturation of synaptic contacts between sensory hair cells and their afferent projections. A better understanding of all these processes could open insights into novel therapeutic strategies aimed to re-establish primary connections from sound transducers to the ascending auditory nerve pathways.


2019 ◽  
Vol 31 (5) ◽  
pp. 898 ◽  
Author(s):  
Peng Zhang ◽  
Wanjun Jiang ◽  
Na Luo ◽  
Wenbing Zhu ◽  
Liqing Fan

The acrosome is single, large, dense-core secretory granule overlying the nucleus of most mammalian spermatozoa. Its exocytosis, the acrosome reaction, is a crucial event during fertilisation. In this study we identified a new acrosome-associated gene, namely IQ motif containing D (IQCD), expressed nearly in multiple tissues with highest expression levels in the testis. In mouse testis, Iqcd transcript accumulated from Postnatal Day (PND) 1 to adulthood. However, expression of IQCD protein at the testicular development stage started primarily from PND 18 and increased in an age-dependent manner until plateauing in adulthood. IQCD was primarily accumulated in the acrosome area of round and elongating spermatids within seminiferous tubules of the testes during the late stage of spermiogenesis; this immunolocalisation pattern is similar in mice and humans. IQCD levels in spermatozoa were significantly lower in IVF patients with total fertilisation failure or a low fertilisation rate than in healthy men. Anti-IQCD antibody significantly inhibited the acrosome reaction and slightly reduced protein tyrosine phosphorylation levels in human spermatozoa, but specifically blocked murine IVF. IQCD interacted with mammalian homolog of C. elegans uncoordinated gene 13 (Munc13) in spermatozoa and may participate in acrosome exocytosis. In conclusion, this study identified a new acrosomal protein, namely IQCD, which is involved in fertilisation and the acrosome reaction.


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