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).
Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.
Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
12.12.2017 | Earth Sciences
12.12.2017 | Power and Electrical Engineering
12.12.2017 | Life Sciences