How ‘Grip-And-Slip’ Wires Up The Brain

Scientists in Japan have discovered how axons respond to cues in the environment to change their direction of migration.

AsianScientist (Mar. 6, 2018) – In a study published in the Proceedings of the Natural Academy of Sciences, scientists in Japan have identified a protein that is crucial for directed axon migration and proper brain development.

Axons sprout from neurons and then migrate to specific parts of the developing brain where they interact with other neurons to form neural networks. The axons move in response to gradients of attractants with extraordinary sensitivity; the sudden stops and sharp turns they make during their migration resemble cars stopping and turning at an intersection

In this study, scientists at the Nara Institute of Science and Technology, in collaboration with researchers at the Osaka National Hospital and University of Tokyo, reported that the L1 cell adhesion molecule (L1-CAM) is crucial for directed axon migration. As implied by its name, L1-CAM allows neurons to adhere to certain proteins outside the cell in a reversible manner.

This is possible because L1-CAM switches between an immobilized state, or what is known as a ‘grip’ state, and a ‘slip’ state. The researchers found that in the presence of an extracellular protein called laminin, L1-CAM was more frequently in the ‘grip’ state, allowing the axons of neurons to produce four times the traction force as compared to when laminin was absent.

The elevated traction force produced by the neuron allowed it to change the direction of its axon on cue. The scientists further found that disrupting the increased grip ratio compromised the directional migration. Their discovery could explain the pathogenesis of several diseases, such as CRASH syndrome—an assortment of neural disabilities that are all attributed to an underdeveloped brain.

“We examined L1-CAM from a patient with CRASH syndrome in which L1-CAM was mutated. The directional axon migration was disturbed,” said Professor Naoyuki Inagaki, corresponding author of the study.

“L1-CAM controls migration not only in the brain, but also in cancer. Grip-and-slip is a new mechanism that could explain other diseases,” he added.

The article can be found at: Abe et al. (2018) Grip and Slip of L1-CAM on Adhesive Substrates Direct Growth Cone Haptotaxis.


Source: Nara Institute of Science and Technology; Photo: Shutterstock.
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