New synapse type discovered by spatial proteomics

March 31, 2024

Enlarge A neuronal atlas with 30 different protein species at a spatial resolution with which individual proteins can be visualized. | © Caption: Eduard Unterauer. Using the new technique, the scientists were able to create a 3D neuronal cell atlas with single-molecule resolution and discovered a previously unknown type of synapse. In the current study, led by Eduard Unterauer in Jungmann's laboratory at the MPI of Biochemistry and the LMU, the researchers present SUM-PAINT. Focusing on the complex environment of neuronal cells in the brain, the team created the first-ever neuronal atlas with single-molecule resolution for 30 different protein types.

A neuronal atlas with 30 different protein species at a spatial resolution with which individual proteins can be visualized. | © Caption: Eduard Unterauer. Copyright: Unterauer, et. al., Cell March 2024

Researchers led by Ralf Jungmann at the Max Planck Institute (MPI) of Biochemistry and LMU, in collaboration with Eugenio F. Fornasiero and Felipe Opazo, both group leaders at the Department of Neuro- and Sensory Physiology at the University Medical Center Göttingen (UMG) and Helmholtz Munich, have developed a new super-resolution high-throughput imaging method. Using the new technique, the scientists were able to create a 3D neuronal cell atlas with single-molecule resolution and discovered a previously unknown type of synapse. The results of the study were published in the journal Cell.

In the current study, led by Eduard Unterauer in Jungmann's laboratory at the MPI of Biochemistry and the LMU, the researchers present SUM-PAINT. This is a new technological development in super-resolution microscopy that, for the first time, allows very fast and virtually unlimited visualization and mapping of a large number of proteins.

"The complexity of living systems ranges from entire organisms and tissues, to the structure of intricate cellular networks, to the organization and interaction of individual biomolecules. To understand this complexity in its entirety, the position, identity, and interaction of individual biomolecules must be studied simultaneously. Such methods, which combine multiple signals, are called multiplexing methods. Four critical challenges must be overcome to achieve a comprehensive understanding of protein organization: Sensitivity, throughput, spatial resolution and multiplexing capability,” explains Eduard Unterauer, co-first author of the study.

Focusing on the complex environment of neuronal cells in the brain, the team created the first-ever neuronal atlas with single-molecule resolution for 30 different protein types. With improved throughput and multiplexing capabilities, they were able to unravel the complexity of the synaptic protein composition of nearly 900 individual synapses.