Toonen and Schmitz publish in The Journal of Cell Biology

18 June 2013

Ruud Toonen and Sabine Schmitz (FGA) publish in the june 2013 issue of The Journal of Cell Biology. The results on the organization of presynaptic terminals originate from a fruitful collaboration with the group of Prof. Casper Hoogenraad (Utrecht University).

Liprin-α2 promotes presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission.

Nerve cells communicate by controlled fusion of vesicles filled with neurotransmitters at specific contact points, called synapses. This process is vital for proper brain function. Its deregulation is often associated with neurological disorders. The release of neurotransmitters takes place at the active zone, a protein-dense specialization of the presynaptic nerve terminal that controls accurate vesicle fusion. To understand how neurons process and relay information, in-depth knowledge of active zone components and their modulation is essential.

Liprin-α2: a key organizer of the active zone

Schmitz, Toonen and Hoogenraad identified the synaptic scaffold protein Liprin-α2 as a key organizer of the active zone. They show that Liprin-α2 organizes presynaptic ultrastructure and controls synaptic output by regulating the number of release-ready, synaptic vesicles. In the absence of Liprin-α2, synapses become very weak. Efficient communication is lost. The presence of Liprin-α2 at presynaptic sites does not depend on other active zone proteins but is critical for recruitment of several components of the synaptic vesicle release machinery. Liprin-α2 appears to be one of the most upstream organizers of the active zone.

Liprin-α2: an exciting protein

“Liprin-α2 is an exciting protein‚, says Dr. Sabine Schmitz, who currently works at the Luxembourg Center for Systems Biomedicine. “It plays a vital role in controlling the molecular make-up of the active zone. Besides its static functions, we also found that its levels in the active zone are tightly regulated, depending on the brain’s activity and protein degradation via the ubiquitin-proteasome system.“
“The fact that Liprin-α2 provides nerve cells with the necessary plasticity to respond to changes in network activity shows potential for the clinic‚, adds Dr. Ruud Toonen. “In many neurological diseases, brain activity is abnormal. Drugs that would influence the levels of Liprin-α2 might help to normalize the brain activity in such patients.‚

Link to the abstract