Two studies on one protein complex give important insight into role of membrane mechanics in biology and tumour development
Two new studies led by Dr Barbara Ciani use different approaches to show new regulatory mechanisms and functions for the protein complex ESCRT.
ESCRT is necessary for sequestering signalling molecules within membrane compartments, a process that prevents abnormal cell growth.
The first study, published in iScience, demonstrated that the mechanical properties of membranes regulate protein activity in vitro. In collaboration with the University of Leeds, purified ESCRT proteins were used to remodel phospholipid vesicles creating complex 'vesicle-within-a-vesicle' architectures that could be used as scaffolds for artificial cells.
Dr Ciani said: "Though the original aim was to build a tool to create artificial cells, we ended up also discovering a key parameter that governs this complex cellular activity."
ESCRT activity is also key for repairing many cellular membranes, which may rupture both as a consequence of physiological and pathological events.
The second study showed that ESCRT membrane repair activity is crucial to maintain the integrity of the membrane surrounding micronuclei – small genomic structures that are only found in cancer cells.
When a micronucleus ruptures, its DNA content is damaged and can re-integrate into the genome randomly. This event increases genomic instability, the main cause of cancer development.
However, it was also shown that this repair activity does not work well in some ruptured micronuclei. Thus, ESCRT-III appears to be both good cop and bad cop, preventing the occurrence of micronuclei with weak membranes, but also exacerbating DNA damage.
The study, published in Oncogenesis, originates from a collaboration with the Department of Oncology and includes collaborators at the University of Manchester, University of Sydney and the CNR in Rome.