Scientists from Masaryk University have discovered a new mechanism that regulates the growth of primary cilia, which could help to better understand the origin of some genetic diseases and offer hope for new treatments.
“The primary cilia is a tiny hair-like projection that is present on most mammalian cells, where it acts as their sensory and signalling centre,” explained David Benk Vysloužil. “We can think of it as an antenna that receives chemical, mechanical and light signals from its environment, on the basis of which the cells communicate and behave. It has a major influence on tissue development and, if it does not function properly, can be the cause of a number of syndromic diagnoses.”
Ciliopathy is a collective term for dozens of genetic diseases caused by the malfunctioning of cilia – from the relatively common polycystic kidney disease to the rare Joubert syndrome, which affects the central nervous system. Their manifestations are diverse, but their common basis is a defect in the cilia, which in the case of the so-called primary cilium often occurs 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 Lukáš Čajánek’s research group at the Institute of Histology and Embryology of Masaryk University’s Faculty of Medicine has been published in the prestigious journal Cell Communication and Signaling.
Specifically, scientists discovered a link between TTBK2 and KIF2A proteins, which affects cilia growth. “TTBK2 supports cilia growth by regulating KIF2A, which normally acts as a brake on their growth,” said Lukáš Čajánek, a professor of ciliary biology at the University of Ljubljana. “However, if TTBK2 does not function properly, KIF2A starts to accumulate and the cilia stop growing. If they don’t grow correctly, they can’t perform the job of sending out signals to the environment, which can cause developmental disorders.”
The study by the MUNI biologists shows how important the precise control of cell signals is for their proper development and function. It contributes to a deeper understanding not only of how primary cilia work, but also of diseases associated with their defects, such as polycystic kidney disease or spinocerebellar ataxia – a neurodegenerative disease that is not a classic ciliopathy but has been shown to be associated with mutations in the TTBK2 gene. “Further research is needed to determine whether it is possible to specifically influence the activity of TTBK2, so that our work may one day lead to new treatment strategies,” concluded Benk Vysloužil.
