How do cells grow? Scientists discover a new way to control their ‘antennae’

Ciliopathy is an umbrella term for dozens of genetic disorders caused by malfunctioning cilia or cilia - from the relatively common polycystic kidney disease to the rare Joubert syndrome affecting the central nervous system. Their manifestations vary, but their common basis is ciliary defects, which in the case of so-called primary ciliation often occur during embryonic development, although others may not appear until later in life. Scientists have discovered a new mechanism by which cells regulate the growth of primary cilia. The discovery by the research group of Lukáš Čajánek from the Deaprtment of Histology and Embryology at the Masaryk University Faculty of Medicine was published in the prestigious journal Cell Communication and Signaling.

"The primary cilia is a tiny hair-like protrusion that is present on most mammalian cells, where it functions as their sensory and signalling centre," explains Mgr. David Benk Vysloužil. "We can think of it as an antenna that receives chemical, mechanical and light signals from its surroundings, on the basis of which cells communicate and behave. It has such a great influence on tissue development and if it is not functioning properly, it can be the cause of many syndromic diagnoses." The discovered mechanism could thus be the key to developing new treatments for patients suffering from one of these rare genetic diseases in the future.

Specifically, the researchers discovered a relationship between the TTBK2 gene, or the protein of the same name that it encodes, and its effect on the KIF2A protein through phosphorylation, a key process in controlling cellular activity through proteins. However, the role of KIF2A in cilia growth has not yet been fully understood. "We found that TTBK2 promotes cilia growth by regulating KIF2A, which normally acts as a kind of brake on cilia elongation," explains Mgr. "However, if TTBK2 does not work properly, KIF2A starts to accumulate and the growth of cilia stops. And if they don't grow to the right length, they can't even perform their signalling function properly and the cell may not respond to signals from the environment as it should, which can lead to developmental disorders."

A study by cell biologists in Brno shows how important precise control of cell signals is for their proper development and function. It is a contribution to a deeper understanding of how not only primary cilia function, but also to the understanding of diseases that are associated with their defects, such as polycystic kidney disease or spinocerebellar ataxia - a neurodegenerative disease that, although not a classical ciliopathy, has been shown to be associated with mutations in the TTBK2 gene. "Further research is therefore needed to see if TTBK2 activity can be targeted so that our work may one day lead to new treatment strategies," concludes Benk Vysloužil.