Molecular Evolution of CatSper in Mammals and Function of Sperm Hyperactivation in Gray Short-Tailed Opossum

Males have evolved species-specifical sperm morphology and swimming patterns to adapt to different fertilization environments. In eutherians, only a small fraction of the sperm overcome the diverse obstacles in the female reproductive tract and successfully migrate to the fertilizing site. Sperm arriving at the fertilizing site show hyperactivated motility, a unique motility pattern displaying asymmetric beating of sperm flagella with increased amplitude. This motility change is triggered by Ca2+ influx through the sperm-specific ion channel, CatSper. However, the current understanding of the CatSper function and its molecular regulation is limited in eutherians. Here, we report molecular evolution and conservation of the CatSper channel in the genome throughout eutherians and marsupials. Sequence analyses reveal that CatSper proteins are slowly evolved in marsupials. Using an American marsupial, gray short-tailed opossum (Monodelphis domestica), we demonstrate the expression of CatSper in testes and its function in hyperactivation and unpairing of sperm. We demonstrate that a conserved IQ-like motif in CatSperζ is required for CatSperζ interaction with the pH-tuned Ca2+ sensor, EFCAB9, for regulating CatSper activity. Recombinant opossum EFCAB9 can interact with mouse CatSperζ despite high sequence divergence of CatSperζ among CatSper subunits in therians. Our finding suggests that molecular characteristics and functions of CatSper are evolutionarily conserved in gray short-tailed opossum, unraveling the significance of sperm hyperactivation and fertilization in marsupials for the first time.

Mechanical Durotactic Environment Enhances Specific Glioblastoma Cell Responses

Background: A hallmark of glioblastoma is represented by their ability to widely disperse throughout the brain parenchyma. The importance of developing new anti-migratory targets is critical to reduce recurrence and improve therapeutic efficacy. Methods: Polydimethylsiloxane substrates, either mechanically uniform or presenting durotactic cues, were fabricated to assess GBM cell morphological and dynamical response with and without pharmacological inhibition of NNMII contractility, of its upstream regulator ROCK and actin polymerization. Results: Glioma cells mechanotactic efficiency varied depending on the rigidity compliance of substrates. Morphologically, glioma cells on highly rigid and soft bulk substrates displayed bigger and elongated aggregates whereas on durotactic substrates the same cells were homogeneously dispersed with a less elongated morphology. The durotactic cues also induced a motility change, cell phenotype dependent, and with cells being more invasive on stiffer substrates. Pharmacological inhibition of myosin or ROCK revealed a rigidity-insensitivity, unlike inhibition of microfilament contraction and polymerization of F-actin, suggesting that alternative signalling is used to respond to durotactic cues. Conclusions: The presence of a distinct mechanical cue is an important factor in cell migration. Together, our results provide support for a durotactic role of glioma cells that acts through actomyosin contractility to regulate the aggressive properties of GBM cells.

Group formation and cohesion of active particles with visual perception–dependent motility

Group formation in living systems typically results from a delicate balance of repulsive, aligning, and attractive interactions. We found that a mere motility change of the individuals in response to the visual perception of their peers induces group formation and cohesion. We tested this principle in a real system of active particles whose motilities are controlled by an external feedback loop. For narrow fields of view, individuals gathered into cohesive nonpolarized groups without requiring active reorientations. For wider fields of view, cohesion could be achieved by lowering the response threshold. We expect this motility-induced cohesion mechanism to be relevant not only for the self-organization of living systems, but also for the design of robust and scalable autonomous systems.