Medical Research Council - London Institute of Medical Sciences

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Disrupted Delivery

Disrupting protein trafficking in the brain can lead to behavioural changes - a mouse model of a human genetic disorder

02 May 2021

Disrupted Delivery

Inside each cell, a fleet of delivery vehicles ferry packages from A to B, ensuring proteins and nutrients are efficiently deposited where they are needed most. Any malfunction of these transporters, called endosomes, can cause traffic jams and protein pileups. WASHC4 (green in the mouse brain section pictured) is a protein involved in endosome trafficking, and previous research has shown that children with a genetic mutation affecting this protein have trouble learning. To investigate, researchers replicated this mutation in mice. The mice developed fewer WASHC4 proteins, oversized endosomes, and an excess of proteins that break down material, causing a build up of debris. The mice with this disrupted delivery system showed learning difficulties and developed movement problems that worsened with age, also found in patients with the mutation. Understanding the molecular basis for the physical symptoms could lead to new approaches to treatment or, even better, prevention.

Written by Anthony Lewis

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