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).
Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
08.12.2016 | Materials Sciences
08.12.2016 | Materials Sciences
08.12.2016 | Physics and Astronomy