According to an article published in the October 8, 2014 edition of the journal eLIFE, research scientists at Helmholtz Zentrum München and the Institute of Diabetes and Regeneration Research (IDR) have discovered the protein Flattop, which regulates the asymmetric positioning of cilia. Malfunctions in this process lead to different clinical phenotypes, and diseases of the sensory or motile cilia play a key role in deafness, lung diseases or diabetes.
Cilia – small, hair-like, microtubule-based structures – project from the basal body (BB) and are precisely positioned on many of the epithelial cells. It has never been clear how proteins regulate planar cell polarity (PCP) or the positioning of the basal body (BB) and cilia. Researcher Moritz Gegg of Helmholtz Zentrum München, and Professor Heiko Lickert of IDR have now taken an important step in elucidating this mechanism.
“Epithelial cell layers line all of the inner and outer body and organ surfaces in the human body, for example in the lung, intestine, pancreas and in the inner ear,” said Moritz Gegg, PhD.
“Only through this exact positioning can cilia movements be coordinated so precisely that for example mucus can be transported from the lung or sound can be perceived from sensory inner ear hair cells,” said Heiko Lickert, PhD.
Cilia are anchored by the basal bodies to the plasma membrane and like many other organelles must be localized to a specific position in a cell. To ensure this, the PCP machinery goes into action. It orients organelles in single cells, but also determines the position of these cells within the plane of an epithelial layer. A complete loss of this cell polarity machinery can lead to very severe developmental disorders, such as chronic bronchitis, deafness or other birth defects.
“Further studies are needed to elucidate exactly how the protein complex consisting of Fltp, Dlg3, the core PCP proteins and the basal body proteins interacts with the cytoskeleton,” said Gegg. “In addition, the important question needs to be clarified as to what extent this protein complex also fulfills a similar function in other epithelial cell types.”
Gegg, M.et al. (2014), Flattop regulates basal body docking and positioning in mono- and multiciliated cells. eLife 2014;10.7554/eLife.03842.
Source: Helmholtz Zentrum München, and the Institute of Diabetes Regeneration Research (IDR)