Yuki, S. | Search bioRxiv

bioRxiv2024

Evolution of invertebrate Cdk4/6-Cdkn2 system

The cell cycle is driven by cyclin-dependent kinases (Cdks). The decision whether the cell cycle proceeds is made during G1 phase, when Cdk4/6 functions. Cyclin-dependent kinase inhibitor 2 (Cdkn2) is a specific inhibitor of Cdk4/6, and their interaction depends on D84 in Cdkn2 and R24/31 in Cdk4/6. This knowledge is based mainly on studies in mammalian cells. Here, we comprehensively analyzed Cdk4/6 and Cdkn2 in invertebrates and found that Cdk4/6 was present in most of the investigated phyla, but the distribution of Cdkn2 was rather uneven among and within the phyla. The positive charge of R24/R31 in Cdk4/6 was conserved in all analyzed species in phyla with Cdkn2. The presence of Cdkn2 and the conservation of the positive charge were statistically correlated. We also found that Cdkn2 has been tightly linked to Fas associated factor 1 (Faf1) during evolution. We discuss potential interactions between Cdkn2 and Cdk4/6 in evolution and the possible cause of the strong conservation of the microsynteny.

evolutionary biology↗

bioRxiv2022

Simulation of the effect of the randomness of climbing fiber input on the relationship between motor learning and Focal Task-Specific Dystonia

Focal Task-Specific Dystonia (FTSD) is an intractable neurological disorder with no clear prevention or treatment that affects more than 1% of classical musicians and threatens the active lives of experts due to its task-specific tremor symptoms. In the present study, we focused on the motor learning function of the cerebellum, which has not been the focus of much attention in the past. We numerically simulated the firing of cerebellar Purkinje cells and cerebellar nuclei during eyeblink conditioning as a typical example of cerebellar-related timing motor learning, with the aim to find the principle of the pathogenesis of FTSD at the level of individual neurons. The results showed the sustained firing of cerebellar nuclei after the learning condition in which the climbing fiber input to Purkinje cells was continued randomly. Therefore, the present study claims a suggestive factor regarding the neural mechanism of the cerebellum in the motor learning-induced task-specific tremor, which is a symptom of FTSD. We also proposed a motor learning paradigm, "undesirable motor learning," in which the motor goal is too advanced to be achieved by repetitions alone and converges to a different result than the desired.

neuroscience↗