What is missing in a neuron

Connections within the brain

New insights into the formation of nerve fiber connections

Proteins, especially the protein called SIP1, play a crucial role in the formation of connections between nerve cells. If it is absent, the growth and branching of the nerve fibers are delayed. The result: diseases that are associated with motor and mental impairments, such as Mowat Wilson Syndrome. Scientists at Charité - Universitätsmedizin Berlin have now further elucidated the underlying molecular mechanism. The results of the current study are in the specialist magazine Neuron * released.

Language, mathematics, art, communication - these and many other services are made possible by the human brain with its highly complex structure. It is crucial that the nerve cells are properly networked with one another. Billions of neurons exchange information via nerve fiber connections called axons and dendrites. If these connections are missing or if they are poorly developed due to developmental disorders, serious impairments of intellectual or physical abilities occur. The protein SIP1 is encoded by the gene of the same name and initiates the functions of a number of other genes. At the molecular level, SIP1 influences the formation of neuronal connections. The researchers around Prof. Dr. Victor Tarabykin, Director of the Institute for Cell and Neurobiology, has now succeeded in demonstrating this direct connection in an animal model.

Cell components, the microtubules, are required to form nerve fiber connections. These form an intracellular framework that gives cells their characteristic shape. Microtubules are also auxiliary molecules for numerous cellular functions. In neurons, the protein SIP1 activates the production of another protein called ninein. The protein ninein in turn binds microtubules within the axons and stabilizes these structures. "In the presence of ninein, the microtubule scaffold can be built up effectively and thus enable the nerve connections to grow," explains Swathi Srivatsa, first author of the study. “If SIP1 is missing, however, the level of nine in the neuron is also reduced. As a result, microtubules are destabilized and more likely to break down, which leads to reduced growth and less branching of the axon. ”Ultimately, important neuronal connections are not formed. In the worst case, entire bundles of axonal lines between different regions of the brain are missing or the connection between the two halves of the brain or to the spinal cord is not established. These current findings contribute to a better understanding of the molecular processes involved in the development of the brain and its connections, as well as paving the way for future studies.

* Swathi Srivatsa, Srinivas Parthasarathy, Zoltán Molnár and Victor Tarabykin. Sip1 downstream effector ninein controls neocortical axonal growth, ipsilateral branching and microtubule growth and stability. Neuron, March 2015. doi: 10.1016 / j.neuron.2015.01.018


Institute for Cell and Neurobiology


Prof. Dr. Victor Tarabykin
Director of the Institute for Cell and Neurobiology
Charité - University Medicine Berlin
t: +49 30 450 528 418

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