A team of scientists at the University of California, San Diego School of Medicine have identified a network of genes that initiate and manage cilia formation. Although scientists have known about cilia for decades, only recently have they discovered their role in disease. This new discovery, which may lead to new therapies for ciliopathies, will appear in the April 15 edition of Nature.
Primary cilia are small, hair-like appendages attached to the surface of human cells. They act like antennae, sensing and evaluating extracellular signals to coordinate the development and stability of a wide variety of organs. Ciliopathies are a newly emerging group of genetic diseases caused by defects in the function or structure of cellular primary cilia. These diseases present symptoms such as mental retardation, retinal blindness, obesity, polycystic kidney disease, liver fibrosis, ataxia and some forms of cancer.
The scientists, led by Joe Gleeson, MD, professor of neurosciences and pediatrics at UC San Diego and a Howard Hughes Medical Institute Investigator, and Joon Kim, a UC San Diego postdoctoral fellow, utilized a high-throughput, cell-based screen to evaluate the impact of more than 8,000 genes and their relation to cilia function and development.
"Utilizing high-throughput screening, we were able view a wider array of the genes implicated in ciliopathies and enact systematic approaches, which enabled us to gain deeper insight into the molecular mechanisms of cilia formation," said Gleeson.
Additional investigation revealed that the endocytic recycling pathway, which absorbs and processes plasma membrane, also plays a key role in primary cilia formation. The scientists also identified protein groups that are key modulators between cilia and the endocytic recycling pathway. These findings suggest that there are specific protein targets for the development of ciliopathy therapy, according to Gleeson.
When cytochalasin D, a small molecule which permeates cells and inhibits cytoskeleton polymerization, was applied to one of the identified proteins, it repaired cilium formation in cells carrying mutations.
"While the use of cytochalasin D is not a viable solution in patients because of its toxicity, we now know that pharmacological solutions for ciliopathy exist," said Kim.
The research team intends to continue searching for "cleaner" small molecules, which can be utilized for ciliopathy treatment.
Additional contributors to the study include Ji Eun Lee of UC San Diego, School of Medicine, Department of Neurosciences; Keiichiro Ono, KiYoung Lee, and Trey Ideker of UC San Diego School of Medicine and Bioengineering; Susanne Heynen, Eigo Suyama, and Pedro Aza-Blanc of Sanford-Burnham Institute for Medical Research.
This study was funded in part by the National Institutes of Health, the National Alliance for Research on Schizophrenia and Depression, and the Howard Hughes Medical Institute.
Jamee Lynn Smith | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences