INTRODUCTION: Angiomotin-like 1 (AMOTL1) belongs to the angiomotin family of proteins which functions have been primarily characterized in vertebrate epithelial cells: the proteins regulate adhesive contacts, cell migration, polarization, and activity of the HIPPO pathway. However, the function of AMOTL1 in the central nervous system remains widely unknown. To characterize the role of AMOTL1 in the brain we generated a systemic knock-out mice (AMOTL1 KO) in which we observed a locomotor hyperactivity, an increased turning behavior, a decreased anxiety, and sensitivity to a low dose of amphetamine – most of the phenotypes can be linked with mouse models of different neuropsychiatric disorders.

AIM(S): The aim of the study was to characterize the functions of AMOTL1 in the brain.

METHOD(S): We performed a set of experiments using primary neurons cultures. It allowed to describe the morphological features of the neurons. Additionally, using tissue samples, we quantified the neurotransmitters of interest level via immunoenzymatic approach, as well as we immunodetected by Western blot the amount of specific proteins. The genes of interest expression has been quantified by RT-qPR.

RESULTS: Our experiments demonstrate that AMOTL1 plays important functions in the central nervous system. We identified important centers in the brain where AMOTL1 appears to have critical functions and discovered that lack of AMOTL1 leads to altered synaptic organization and neurotransmitters alterations. The changes were associated with behavioral impairments of mutant mice observed in various behavioral tests. Collectively, our studies highlight AMOTL1 as a potential key player in regulating pathological processes observed in various neuropsychiatric disorders.

CONCLUSIONS: The study clearly demonstrates the importance of AMOTL1 in proper functioning of the brain. We characterized behavioral abnormalities in AMOTL1 mutant mice and provided results revealing potential molecular and cellular causes.

FINANCIAL SUPPORT: The work was supported by the Polish National Science Centre, NCN grant 2019/33/B/NZ3/02528.