During neural development, newborn neurons extend axons toward distant targets then form connections with other cells. This process depends on the growth cone, a dynamic structure at the growing axon tip of the neuron that detects attractive and repulsive guidance cues. Many axon guidance molecules have been identified, and their functions are well characterized, but exactly how they cause growth cone turning has been unclear.
Hiroyuki Kamiguchi of the RIKEN Brain Science Institute, Wako, and his colleagues have now shown that repulsive growth cone turning is driven by a process called endocytosis1, whereby portions of the growth cone’s membrane are removed and internalized.
Endocytosis occurs continuously in all neurons to remove receptors and other membrane proteins for recycling, and to take-up neurotransmitters after their release. It is mediated by a molecule called clathrin, which induces formation of spherical ‘pits’ in the membrane that are then pulled into the cell.
By tagging clathrin with a fluorescent marker and observing the cells under a microscope, Kamiguchi’s group visualized the formation and movements of pits in the growth cones of dorsal root ganglion cells from embryonic chicks. They observed pits appearing at the edges of the growth cones that then migrated towards the center. Pit migration was significantly slowed by blebbistatin, a small molecule that inhibits the motor protein myosin II, which moves a structure called the cytoskeleton towards the growth cone center, suggesting that pits are coupled with cytoskeletal flow.
The researchers then induced localized increases of calcium ion concentrations in the growth cones, mimicking their response to repulsive guidance cues. On the side where calcium was elevated, asymmetrical endocytosis resulted and turned the growth cones the other way.
When Kamiguchi and colleagues added compounds that inhibit endocytosis, however, they abolished repulsive turning in response to either increased calcium concentration or repulsive axon guidance molecules. In contrast, they showed that inducing asymmetric endocytosis in the absence of guidance cues and localized increases of calcium concentration was sufficient to cause growth cone turning.
They also calculated that endocytosis removes at least 2% of the growth cone membrane every minute, corresponding to 72% of the total surface area during the entire course of turning.
“We now know that repulsive turning depends on asymmetric endocytosis of adhesion molecules from the growth cone surface,” says Kamiguchi, “but we think it also requires many other unidentified molecules to be internalized and recycled.” The team is conducting large-scale analyses to find them.
The corresponding author for this highlight is based at the Laboratory for Neuronal Growth Mechanisms, RIKEN Brain Science Institute
Journal information1. Tojima, T., Itofusa, R. & Kamiguchi, H. Asymmetric clathrin-mediated endocytosis drives repulsive growth cone guidance. Neuron 66, 370–377 (2010).
gro-pr | Research asia research news
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences