Tsai studies a kinase (kinases are enzymes that change proteins) called Cdk5. While Cdk5's best-known role is to help new neurons form and migrate to their correct positions during brain development, "emerging evidence supports an important role for Cdk5 at the synapse," she said.
To gain a better understanding of how Cdk5 promotes synapse formation, Tsai's lab looked into how Cdk5 interacts with synapse-inducing proteins-in particular, a protein called CASK. CASK--a key scaffolding protein-is one of the first proteins on the scene of a developing synapse.
Scaffolding proteins such as CASK are like site managers, supporting protein-to-protein interactions to ensure that the resulting architecture is sound. Mutations in the genes responsible for Cdk5 and CASK have been found in mental retardation patients.
"We found that Cdk5 is critical for recruiting CASK to do its job for developing synapses," Tsai said. "Without Cdk5, CASK was not in the right place at the right time, and failed to interact with essential presynaptic components. This, in turn, led to problems with calcium influx." The flow of calcium in and out of neurons affects processes central to nervous system development and plasticity--its ability to change in response to experience.
Gene mutations and/or deletions in synaptic cell surface proteins and molecules called neurexins and neuroligins have been associated with autism. The problem with CASK recruitment investigated by the Tsai laboratory creates the same result as these genetic changes.
The Picower study also provides the first molecular explanation of how Cdk5, which also may go awry in neurodegenerative diseases such as Alzheimer's, promotes synapse development.
"There are still a lot of unknowns," said Tsai, who is also a Howard Hughes Medical Institute investigator. "Causes for psychiatric disorders are still very unclear, but accumulating evidence strongly suggests that alterations in the synaptogenesis program can lead to these serious diseases."
In addition to Tsai and Picower researcher Benjamin A. Samuels, co-authors are associated with Harvard Medical School; Johns Hopkins University School of Medicine; McLean Hospital in Belmont, Mass.; and Academia Sinica in Taiwan.
This work is supported by the National Institute of Neurological Disorders and Stroke (NINDS).
Written by Debbie Halber, Picower Institute for Learning and Memory at MIT
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction