纤毛紊乱症发病机理之重要线索被发现

Scientists led by Dr. Heiko Lickert, research group leader at the Institute of Stem Cell Research of Helmholtz Zentrum München, have identified the first gene shown to regulate cilia（纤毛，睫毛） disassembly in a living organism. If the gene is defective（有缺陷的，不完美的） , double and forked cilia develop – thus the name Pitchfork. The consequences of the mutation include typical defects in the left-right asymmetry（不对称） of body organs and heart failure. The functional investigations were conducted primarily on the mouse model, together with the Institute of Developmental Genetics and the Department of Protein Analytics of Helmholtz Zentrum München. However, Dr. Lickert and his collaboration partner Nicolas Katsanis of Duke University in the U.S. were also able to show mutations in the Pitchfork gene in patients with ciliary diseases. In humans, the substitution of merely one amino acid（氨基酸） in the Pitchfork protein can lead to an inversed（倒生的） position of all internal organs (situs inversus内脏逆位), to kidney and liver diseases, but also to severe heart defects. "Our study" Dr. Lickert said, "provides a new entry point to understand and categorize ciliary disease."

Background:

Cilia are hair-like cell protuberances, 5 to 10 µm long and 250 nm thick, which are present in almost all human or animal cells. They function like antennas（天线，触角） in the cells and play a pivotal role（关键作用） in the perception of the cellular surroundings and signal transduction（转导，转换） .

Defective cilia usually have genetic causes and severe consequences: In recent years more than 30 diseases could be traced to ciliary dysfunctions（功能紊乱，机能障碍） . These ciliopathies affect numerous organ systems and show diverse clinical symptoms, but the molecular and cellular basis for this is not yet understood. The resulting disorders include developmental defects such as polycystic kidney（多囊肾） , liver and pancreas（胰腺） diseases (incidence 1:800) and also heart defects and adiposity（肥胖） . An increased risk for common diseases such as diabetes or cancer is also very probable. Despite the far-reaching significance of cilia, many aspects of the biology of these organelles are not yet known and many questions remain to be answered. These include the regulation of the body's own processes (homeostasis体内平衡), signal transduction between cells, organ and embryonic development, and the assembly and disassembly of cilia in the different phases of the cell cycle.