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

Abstract

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.

Expression Analysis of Circular RNAs in Young and Sexually Mature Boar Testes

“…Accordingly, testicle-specific genes are expressed in strict accordance with temporal and spatial factors at different developmental stages and participate in the regulation of many aspects of sexual development and function under the action of numerous different factors [ 4 , 5 ]. The normal development of testes requires the regulation of cell-cycle-related genes such as cyclin and cyclin-dependent kinase ( CDK ) [ 6 ] as well as meiosis-related genes such as deleted in azoospermia ( DAZ ) family genes [ 7 ]; stimulated by retinoic acid gene 8 ( STRA8 ) [ 8 ]; synaptonemal complex protein gene; heat shock protein gene ( HSP ); proto-oncogene; spermatogenesis related genes such as transition nuclear protein genes ( TNP ), protamine gene 1( PRM1 ) [ 9 ], tektin gene ( TEKTIN ), cation channel of sperm (CatSper) family genes, and transcription regulators; and apoptosis related genes such as Bax / Bcl-2 (B cell lymphoma-2) family genes, P53 gene [ 10 ], Fas /FasL (Fas Ligand) genes, and c-kit (c kitproto oncogene)/SCF (Stem cell factor) genes.…”

Two-Player Game in a Complex Landscape: 26S Proteasome, PKA, and Intracellular Calcium Concentration Modulate Mammalian Sperm Capacitation by Creating an Integrated Dialogue—A Computational Analysis

“…The PI3K activation leads to an increase in actin polymerization; thus, the G-actin polymerizes, forming long filaments of F-actin [ 3 ]. The F-actin constitutes a barrier for the fusion between the OAM and PM and, when the capacitation progresses, the interposition of F-actin avoids their premature fusion [ 28 , 29 ]. In response to the physiological stimulus represented by contact with proteins of the oocyte ZP, high intracellular calcium concentrations enable the depolymerization of actin, since F-actin breakdown between the membranes is needed to allow the acrosome reaction [ 28 ].…”

An interactive analysis of the mouse oviductal miRNA profiles

“…In keeping with Bernabò et al (Ordinelli et al, 2018;Bernabò et al, 2019), we identified the hubs within Murine Oviductal MiRNome as the nodes with a degree at least one standard deviation above the network mean. In details, the hubs were identified based on the following formula:…”