Scientists have identified a new role for a protein complex at the center of a human genetic disorder called Bardet-Biedl syndrome, or BBS, for which there is currently no cure.
Bardet-Biedl syndrome arises when the BBSome protein complex malfunctions. Because the BBSome regulates the form and function of cilia, the hair-like structures on the surface of cells, BBS has been classified as a disease of the cilia.
But the wide spectrum of symptoms associated with BBS — the most common of which is vision loss, as well as obesity, extra fingers or toes and kidney malfunction — have led to hypotheses that the cause of the syndrome may not lie solely within the cilia.
In a new study published in Developmental Cell, a team from the University of Michigan Life Sciences Institute now offers the first known direct evidence for these hypotheses. Their findings demonstrate that the BBSome operates outside of cilia to support sight, at least in one common model species.
The discovery began when scientists in the lab of LSI faculty member Shawn Xu were investigating how tiny roundworms called Caenorhabditis elegans can sense light despite having no eye-like organs. Because C. elegans have a simple and well-mapped nervous system, the Xu lab uses them as a model to understand the fundamental biology behind various forms of sensation.
The team performed a genetic screen, a process of introducing random mutations to identify which genes are required for a given biological process, to find the genes involved in the worms’ ability to respond to light. Most of the mutations that caused worms to stop sensing light turned out to be in the BBSome. And, like the progressive vision loss that BBS patients experience, the worms with BBSome mutations progressively lost the ability to sense light as they aged.
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