Researchers discover a key mechanism behind synapse maturation

Laboratory researchers led by Prof. Joris of Wit (Vib-Ku Louven) have discovered an important track about how connections between brain cells, known as synapses, mature. These new findings, published in the development cell, demonstrated how two different proteins, GPR158 and PLCXD2, interact to form a specific component in the synapse development: the spine apparatus.

Synapses, communication points between neurons, are not only molecularly diverse, but also contain specialized organelles, small internal cell machines, which Fineton their function. The column apparatus is one of those organelles, and is essential to stabilize mature synapses and support learning and memory. However, how the neurons control where and when the open questions were asked.

Now, the research team has identified a new synaptic protein complex that regulates the incorporation of the column apparatus into synapse development. His study reveals that a protein called GPR158 interacts with an atypical enzyme, PLCXD2, to control the abundance of column devices and the maturation of the dendritic spines: the small protuberances in neurons that receive synaptic information.

There is a strong evidence that the column apparatus helps amplify communication between neurons acting as a calcium deposit, a function that is crucial for proper maturation of dendritic thorns. ”

Ben Verpoort, first author of the study

Raising the brake in synaptic development: the interaction between GPR158 and PLCXD2

Using a combination of molecular biology and advanced image techniques, the equipment identified PLCXD2, a protein without known function in the brain, as a negative regulator of the formation of spine devices. PLCXD2 alters the local lipid environment within the dendritic spines, interrupting the key sites necessary for assembly of the spine apparatus.

Other experiments revealed that GPR158 works by joining directly and inhibiting PLCXD2. This interaction neutralizes the suppressor effect of PLCXD2, raising the brake on the formation of the spine apparatus, which allows you to assemble correctly.

In the neurons that lack GPR158, the activity PLCXD2 without control led to a marked reduction in the abundance of column devices accompanied by a change to immature synaptic structures. These immature dendritic thorns cannot completely maintain synaptic communication, a finding backed by experiments that show reduced levels of essential receptors of neurotransmitters, critical proteins to transmit signals between neurons.

Surprisingly, eliminating PLCXD2 in these same neurons restored the abundance of column devices and the ripening of the standardized dendritic column, directly linking the maturation defect with the non -opposite activity of PLCXD2.

“We see underdeveloped synapses that probably communicate less effectively, which could have serious consequences for learning and memory training,” explains Ben Verpoort.

Relevance for brain disorders

Understanding how the device is formed and the functions of the column apparatus is especially important because it has been involved in brain disorders such as Alzheimer’s and Autism, where calcium imbalance and deteriorated synaptic signage are key features. This recently identified GPR158 -PLCXD2 axis offers information on how the synaptic structure and receiver content are regulated during brain development and what could go wrong in the disease.

“Understanding how this molecular brake works gives us a new management on synaptic development and plasticity,” says Professor Joris of Wit. “Open exciting ways to study how synapses stabilize or fail in brain connectivity disorders.”