Structure of Neuron-Connecting Synaptic Adhesion Molecules Discovered

Figure 1: Overview of the PTPd Ig1–3/Slitrk1 LRR1 complex. Copyright : Korea Advanced Institute of Science and Technology

A research team has found the three-dimensional structure of synaptic adhesion molecules, which orchestrate synaptogenesis. The research findings also propose the mechanism of synapses in its initial formation.

Some brain diseases such as obsessive compulsive disorder (OCD) or bipolar disorders arise from a malfunction of synapses. The team expects the findings to be applied in investigating pathogenesis and developing medicines for such diseases.

The research was conducted by a Master’s candidate Kee Hun Kim, Professor Ji Won Um from Yonsei University, and Professor Beom Seok Park from Eulji University under the guidance of Professor Homin Kim from the Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), and Professor Jaewon Ko from Yonsei University. Sponsored by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, the research findings were published online in the November 14th issue of Nature Communications.

Figure 2: Representative negative-stained electron microscopy images of Slitrk1 Full ectodomain (yellow arrows indicate the horseshoe-shaped LRR domains). The typical horseshoe-shaped structures and the randomness of the relative positions of each LRR domain can be observed from the two-dimensional class averages displayed in the orange box. Copyright : Korea Advanced Institute of Science and Technology

A protein that exists in the neuronal transmembrane, Slitrk, interacts with the presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) and forms a protein complex. It is involved in the development of synapses in the initial stage, and balances excitatory and inhibitory signals of neurons.

It is known that a disorder in those two proteins cause a malfunction of synapses, resulting in neuropsychosis such as autism, epilepsy, OCD, and bipolar disorders. However, because the structure as well as synaptogenic function of these proteins were not understood, the development of cures could not progress.

The research team discovered the three-dimensional structure of two synaptic adhesion molecules like Slitrk and LAR-RPTPs and identified the regions of interaction through protein crystallography and transmission electron microscopy (TEM). Furthermore, they found that the formation of the synapse is induced after the combination of two synaptic adhesion molecules develops a cluster.

Figure 3: Model of the two-step presynaptic differentiation process mediated by the biding of Slitrks to LAR-RPTPs and subsequent lateral assembly of trans-synaptic LAR-RPTPs/Slitrik complexes. Copyright : Korea Advanced Institute of Science and Technology

Professor Kim said, “The research findings will serve as a basis of understanding the pathogenesis of brain diseases which arises from a malfunction of synaptic adhesion molecules. In particular, this is a good example in which collaboration between structural biology and neurobiology has led to a fruitful result.” Professor Ko commented that “this will give new directions to synaptic formation-related-researches by revealing the molecular mechanism of synaptic adhesion molecules.”

Source: KAIST

The Outsmarting nature during disasters: Instead of winging it, planners need to think carefully about costs and benefits

Natural Disasters

The dramatic images of natural disasters in recent years, including hurricanes Katrina and Sandy and the Tohoku, Japan, earthquake and tsunami, show that nature, not the people preparing for hazards, often wins the high-stakes game of chance.

"We're playing a high-stakes game against nature without thinking about what we're doing," geophysicist Seth Stein of Northwestern University said. "We're mostly winging it instead of carefully thinking through the costs and benefits of different strategies. Sometimes we overprepare, and sometimes we underprepare."

Stein will discuss his research in a presentation titled "How Much Natural Hazard Mitigation is Enough?" at the American Association for the Advancement of Science (AAAS) annual meeting in Chicago. His presentation is part of the symposium "Hazards: What Do We Build For?" to be held Feb. 17.

Stein is the William Deering Professor of Geological Sciences in Northwestern's Weinberg College of Arts and Sciences. He is the author of a new book, "Playing Against Nature: Integrating Science and Economics to Mitigate Natural Hazards in an Uncertain World" (Wiley, 2014) and the book "Disaster Deferred: A New View of Earthquake Hazards in the New Madrid Seismic Zone" (Columbia University Press, 2010).

Sometimes nature surprises us when an earthquake, hurricane or flood is bigger or has greater effects than expected. In other cases, nature outsmarts us, doing great damage despite expensive mitigation measures or causing us to divert limited resources to mitigate hazards that are overestimated.

"To do better we need to get smarter," Stein said. "This means thoughtfully tackling the tough questions about how much natural hazard mitigation is enough. Choices have to be made in a very uncertain world."

Stein's talk will use general principles and case studies to explore how communities can do better by taking an integrated view of natural hazards issues, rather than treating the relevant geoscience, engineering, economics and policy formulation separately.

Some of the tough questions include:

• How should a community allocate its budget between measures that could reduce the effect of future natural disasters and many other applications, some of which could do more good? For example, how to balance making schools earthquake resistant with hiring teachers to improve instruction?
• Does it make more sense to build levees to protect against floods or to prevent development in the areas at risk?
• Would more lives be saved by making hospitals earthquake resistant or by using the funds for patient care?

The choice is difficult because although science has learned a lot about natural hazards, Stein says, our ability to predict the future is much more limited than often assumed. Much of the problem comes from the fact that formulating effective natural hazard policy involves combining science, economics and risk analysis to analyze a problem and explore costs and benefits of different options in situations where the future is very uncertain.

Because mitigation policies are typically chosen without such analysis -- often by a government mandate that does not consider the costs to the affected communities -- the results are often disappointing.


Source: Northwestern University
Summary: The dramatic images of natural disasters, including hurricanes Katrina and Sandy and the Tohoku, Japan, earthquake and tsunami, show that nature, not the people preparing for hazards, often wins the high-stakes game of chance. In a recent presentation, a geophysicist uses general principles and case studies to explore how communities can do better by taking an integrated view of natural hazards issues, rather than treating the relevant geoscience, engineering, economics and policy formulation separately.

Is there an ocean beneath our feet? Ocean water may reach upper mantle through deep sea faults

Parinacota, a volcano on the border of Chile and Bolivia. Credit: © Georges Bartoccioni / Fotolia

Scientists at the University of Liverpool have shown that deep sea fault zones could transport much larger amounts of water from Earth's oceans to the upper mantle than previously thought.

Water is carried mantle by deep sea fault zones which penetrate the oceanic plate as it bends into the subduction zone. Subduction, where an oceanic tectonic plate is forced beneath another plate, causes large earthquakes such as the recent Tohoku earthquake, as well as many earthquakes that occur hundreds of kilometers below Earth's surface.

Seismic modelling
Seismologists at Liverpool have estimated that over the age of Earth, the Japan subduction zone alone could transport the equivalent of up to three and a half times the water of all Earth's oceans to its mantle.
Using seismic modelling techniques the researchers analysed earthquakes which occurred more than 100 km below Earth's surface in the Wadati-Benioff zone, a plane of Earthquakes that occur in the oceanic plate as it sinks deep into the mantle.

Analysis of the seismic waves from these earthquakes shows that they occurred on 1 -- 2 km wide fault zones with low seismic velocities. Seismic waves travel slower in these fault zones than in the rest of the subducting plate because the sea water that percolated through the faults reacted with the oceanic rocks to form serpentinite -- a mineral that contains water.

Some of the water carried to the mantle by these hydrated fault zones is released as the tectonic plate heats up. This water causes the mantle material to melt, causing volcanoes above the subduction zone such as those that form the Pacific 'ring of fire'. Some water is transported deeper into the mantle, and is stored in the deep Earth.

"It has been known for a long time that subducting plates carry oceanic water to the mantle," said Tom Garth, a PhD student in the Earthquake Seismology research group led by Professor Andreas Rietbrock.

"This water causes melting in the mantle, which leads to arc releasing some of the water back into the atmosphere. Part of the subducted water however is carried deeper into the mantle and may be stored there.

Large amounts of water deep in Earth
"We found that fault zones that form in the deep oceanic trench offshore Northern Japan persist to depths of up to 150 km. These hydrated fault zones can carry large amounts of water, suggesting that subduction zones carry much more water from the ocean down to the mantle than has previously been suggested.

"This supports the theory that there are large amounts of water stored deep in the Earth."
Understanding how much water is delivered to the mantle contributes to knowledge of how the mantle convects, and how it melts, which helps to understand how plate tectonics began, and how the continental crust was formed.


Source: University of Liverpool

Summary: Scientists have shown that deep sea fault zones could transport much larger amounts of water from Earth's oceans to the upper mantle than previously thought.