Functions of the AMOTL1 Protein in Dopaminergic and Serotonergic Systems in the Brain – AL1SERDOPA

Our behavior, consciousness, memory, and everyday functioning are made possible by communication between various regions of the brain. This communication is primarily supported by neurons that release neurotransmitters to ensure proper signaling between cells. Distinct neuronal populations release specific neurotransmitters that act on selected groups of neurons equipped with specialized receptors.

Among these neurotransmitters is dopamine, produced by dopaminergic neurons, which is associated with feelings of pleasure and reward. Serotonin, released by serotonergic neurons, regulates mood, sleep, and depression. A remarkable feature of these neuronal populations is that, despite their relatively small numbers, they send projections capable of modulating the activity of most brain regions. The dopaminergic and serotonergic systems are fundamental to the proper functioning of the brain, and disruptions in one or both systems are linked to numerous psychiatric disorders, including substance-use disorders, depression, schizophrenia, bipolar disorder, ADHD, and Parkinson’s disease.

The proposed project aims to characterize the function of a protein called AMOTL1 in the regulation of dopaminergic and serotonergic neurons. To date, the role of AMOTL1 has been studied primarily in cell polarity, adhesion, and cancer progression, but not in the central nervous system. AMOTL1 belongs to the angiomotin family, which also includes AMOT and AMOTL2. These proteins are closely related and share similar domain organization. However, despite their high structural similarity, each angiomotin has unique functions. Importantly, the roles of angiomotins in the brain remain poorly understood.

There are, however, reports suggesting that AMOT regulates neuronal development and maturation. These findings represent only the beginning of understanding the functions of angiomotins in the brain. Our preliminary data indicate that AMOTL1 also plays a significant role in regulating the activity of dopaminergic and serotonergic neurons. Therefore, this project aims to thoroughly investigate the functions of AMOTL1 in these two neurotransmitter systems.

Experiments will be conducted using mice lacking AMOTL1 expression in both neuronal populations. We will examine how AMOTL1 deletion affects neuronal activity. Our studies will include behavioral analyses, brain tissue examination, and molecular assessments to comprehensively understand the functions of AMOTL1 in both neuron types. Neurological dysfunctions and disturbances in brain processes represent major challenges for healthcare systems. With support from the National Science Centre (NCN), the results obtained in this project may contribute to the development of new therapeutic strategies for neurological disorders.