Earmarked for destruction
Brain cells routinely destroy the supply of molecules that support their connections with other brain cells.
Our brain contains billions of cells called neurons that form an extensive network through which information is readily exchanged. These cells connect to each other via junctions called synapses. Our developing brain starts off with far more synapses than it needs, but the excess synapses are destroyed as the brain matures. Even in adults, synapses are continuously made and destroyed in response to experiences and learning.
Inside neurons there are tiny bubble-like compartments called vesicles that supply the synapses with many of the proteins and other components that they need. There is a growing body of evidence that suggests these vesicles are rapidly destroyed once a synapse is earmarked for destruction, but it is not clear how this may occur.
Beyenech Binotti, Nathan Pavlos and co-workers found that a protein called Rab26 sits on the surface of the vesicles near synapses. This protein promotes the formation of clusters of vesicles, and a membrane sometimes surrounds these clusters. Further experiments indicate that several proteins involved in a process called autophagy — where unwanted proteins and debris are destroyed — may also be found around the clusters of vesicles.
Autophagy starts with the formation of a membrane around the material that needs to be destroyed. This seals the material off from rest of the cell so that enzymes can safely break it down. Binotti, Pavlos and co-workers found that one of the autophagy proteins — called Atg16L — can bind directly to Rab26, but only when Rab26 is in an ‘active’ state.
These findings suggest that excess vesicles at synapses may be destroyed by autophagy. Further work will be required to establish how this process is controlled and how it is involved in the loss of synapses.
To find out more
Read the eLife research paper on which this story is based: “The GTPase Rab26 links synaptic vesicles to the autophagy pathway” (February 2, 2015).
eLife is an open-access journal that publishes outstanding research in the life sciences and biomedicine.