Research Highlight

Membrane cutting protein plays key role in neuron pruning

05/03/15

Researchers from the MRC Centre for Developmental Neurobiology (CDN), Institute of Psychiatry, Psychology & Neuroscience (IoPPN), have identified a family of proteins that is essential for cutting neuronal branches during pruning.

During development individual neurons grow exuberantly, often generating many more branches than required. A significant number of aberrant or redundant branches are severed and undergo local degeneration during circuit maturation. This‘cutting back’ of branches is essential for properly wiring together the nervous system.

“Neuron trees need to be shaped and adjusted to fit their purpose and pruning is an important way of doing that. The branch severing we see during pruning reminded us of the event that takes place at the end of cell division when a thin tether linking the dividing cells is cut by the a family of proteins called ‘ESCRTs’ ”said Dr. Darren Williams, Senior Lecturer in the MRC CDN and senior author of the study.

Studies in the fruitfly Drosophila have contributed greatly to a deeper understanding of the molecular mechanisms of neuron pruning but the mechanism that controls the cutting of a branch from the parent neuron has remained somewhat elusive. To address this question the Williams lab looked to see if the proteins used at the final steps of cell division were used in neuron pruning. In particular the study looks at one of the protein complexes, the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, which is known to be involved in various biological membrane-cutting events.

“We found the ESCRT machinery in neuronal branches close to the site where branches are cut. Excitingly, when we removed a protein called Shrub, a key component in this complex, branches remained attached by a very thin tether, suggesting this machinery is deployed during pruning to control the branch cutting event.”

This study shows that the ESCRT machineryis required during the developmental pruning of neurons in Drosophila , and provides important insights into the events leading up to branch severing.

Original publication : Loncle N, Agromayor M, Martin-Serrano J, Williams DW 1. An ESCRTmodule is required for neuron pruning. Sci Rep. 2015 Feb13;5:8461. DOI: http://www.nature.com/srep/2015/150213/srep08461/full/srep08461.html

This work was funded by a Wellcome Trust Project Grant and the Medical Research Council.