Another mystery of the human body has been solved by scientists who have identified how a molecular motor essential for human development works. They have also pinpointed why mutations in genes linked to this motor can lead to a range of human diseases.
Researchers at the University of Bristol have defined the composition of the human version of a molecular motor, called 'cytoplasmic dynein-2', that is essential for normal human development. Dynein 2 directs molecules into cilia as well as controlling their movement along cilia.
Cilia are slender protrusions that act as antennae on nearly all human cells. They are important in sensing signals that direct cell function.
Dysfunctional cilia are known to underlie a number of often chronically disabling and sometimes life-threatening genetic conditions. They affect multiple systems, causing blindness, deafness, chronic respiratory infections, kidney disease, heart disease, infertility, obesity and diabetes.
These human diseases are collectively known as ciliopathies, many of which, including Jeune Syndrome, are linked to childhood development.
In the UK, one in every 100,000 babies is born with Jeune Syndrome - a rare genetic disorder that affects the way a child's cartilage and bones develop.
The new research, funded by the Medical Research Council and published today [09 September] in the Journal of Cell Science, has explained exactly how the human cytoplasmic dynein-2 motor works for the first time.
This new knowledge could help with diagnosis and, in the long-term, scientists hope that they might be able to alter the function of the defective motor for therapeutic benefit.
Professor David Stephens, from the School of Biochemistry at the University of Bristol, led the research.
He said: "The discovery of new components of the motor gives us a great opportunity to work towards understanding how defects in dynein-2 lead to disease."
Building on work done in simple model organisms such as green algae, researchers have also shown that two genes associated with Jeune Syndrome (WDR34 and WDR60) are essential parts of the human form of this motor.
Both genes encode proteins required to form a functional dynein-2 motor, explaining why a mutation in either one leads to a ciliopathy.
The work also identified a novel component of dynein-2 (TCTEX1D2), providing another candidate gene that could be mutated in cases of Jeune Syndrome.
'Subunit composition of the human cytoplasmic dynein-2 complex' by David Asante, Nicola L. Stevenson and David J. Stephens in the Journal of Cell Science.
More information on ciliopathies can be found on the Ciliopathy Alliance website.
About the Medical Research Council (MRC)
The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.