The complex inner wiring of the brain is coordinated in part by chemical guidance factors that help direct the interactions between individual neurons. As growing cells extend their axons outward, these tendrils are simultaneously drawn in the correct direction by attractive signals and steered away from ‘wrong turns’ by repulsive signals.
New work from a team led by Hiroyuki Kabayama and Katsuhiko Mikoshiba of the RIKEN Brain Science Institute in Wako has revealed insights into how one of these repulsive guidance cues, semaphorin 3A (Sema3A), gives axons their marching orders. In an earlier study, the researchers found evidence that Sema3A causes large-scale internalization of the cellular membrane at the growth cone, the tip of the growing axon, and determined that this internalization occurs via a process known as macropinocytosis. “These findings suggested an important role for massive, macropinocytosis-mediated membrane retrieval during Sema3A-induced growth cone collapse,” says Kabayama.
The neurotoxin C1, a protease enzyme, induces similar effects on growth cones, and Kabayama and Mikoshiba and their colleagues were able to uncover Sema3A’s mode of action via experiments using this enzyme. Based on a series of experiments with cultured neurons isolated from chick embryos, the researchers determined that the enzyme works by breaking down syntaxin 1B (Syx1B), a protein with a prominent role in membrane trafficking, thereby releasing an inhibitory mechanism that otherwise keeps macropinocytosis in check.
Accordingly, direct inhibition of Syx1B expression in neurons led to reduced axonal growth and increased growth cone collapse. On the other hand, treatment with the macropinocytosis-inhibiting compound EIPA countered the growth cone-collapsing effects of either neurotoxin C1 or inhibition of Syx1B. The researchers also found that this drug alone was sufficient to undermine Sema3A’s axon-repulsive effects
Kabayama, Mikoshiba and colleagues obtained additional confirmation of the central role of Syx1B in experiments that revealed that the treatment of neurons with Sema3A triggers rapid degradation of this protein as a prelude to the initiation of macropinocytosis. This effect could be countered by forcing these cells to overexpress Syx1B. Kabayama also notes that another repulsive signal, ephrin A2, appears to act via the same cellular mechanism. “It is likely that repulsive axon guidance is generally mediated by syntaxin 1B-regulated macropinocytosis,” he says.
In future studies, Kabayama and Mikoshiba intend to test this hypothesis by manipulating this pathway in transgenic animals. “We are going to generate Syx1B-overexpressing mice and investigate whether inhibition of macropinocytosis by Syx1B can prevent ephrin A2- or Sema3A-dependent growth cone collapse,” says Mikoshiba.
The corresponding author for this highlight is based at the Laboratory for Developmental Neurobiology, RIKEN Brain Science InstituteReferences
Kabayama, H., Nakamura, T., Takeuchi, M., Iwasaki, H., Taniguchi, M., Tokushige, N. & Mikoshiba, K. Ca2+ induces macropinocytosis via F-actin depolymerization during growth cone collapse. Molecular and Cellular Neuroscience 40, 27–38 (2009).
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy