Functions of the Amotl2 Protein in the Central Nervous System – AMOTL2

The main function of the central nervous system (CNS) is to receive stimuli from both external and internal environments, process them, and generate appropriate responses. It is responsible for complex cognitive processes, including thinking, learning, and memory. The basic structural and functional unit of the CNS is the neuron, consisting of a cell body, a single long axon, and multiple dendrites. Dendrites collect information from other cells, while axons transmit signals to other neurons. The transmission of information between cells occurs through synapses, specialized junctions that modulate signal flow. Proper synaptic function and neuronal network organization are essential for efficient communication within the CNS. Disruptions in synapse formation and dendritic organization are characteristic of several severe neuropsychiatric disorders, such as schizophrenia, Rett syndrome, and autism.

The aim of this project is to characterize the function of a novel protein, Amotl2, in neurons and the CNS. To date, Amotl2 has primarily been studied in the context of cell polarization, adhesion, and tumorigenesis. Its role in the brain remains unexplored, making this research highly innovative. Amotl2 belongs to the Angiomotin protein family, which also includes Amot and Amotl1. These proteins share a similar domain organization and exhibit functional similarities. While little is known about the role of Angiomotins in the brain, previous studies have shown that Amot regulates dendrite and synapse development, and preliminary findings from the research team indicate that Amotl1 may be linked to psychiatric disorders.

Early results suggest that Amotl2 also plays an important role in synaptic regulation. The project will therefore systematically investigate Amotl2 interactions with other neuronal proteins using biochemical assays on purified proteins. It will also analyze morphological and molecular changes in neurons lacking the Amotl2 gene, as well as assess behavioral phenotypes in mice with neuron-specific Amotl2 deletion.

Given that neurological and brain function disorders represent one of the greatest challenges for modern healthcare, understanding the behavioral, structural, and molecular alterations resulting from Amotl2 deficiency could contribute to the development of new therapeutic strategies for neurological diseases. The project will employ cutting-edge experimental techniques, and the expected findings have the potential to make a significant contribution to the understanding of neuronal and brain biology.