Nanobiology of the primary cilium--paradigm of a multifunctional nanomachine complex.
Of all the organelles in the eukaryotic cells, it is argued that the primary cilium is a paradigm in terms of nanomachinery found in the living cell. The components that are brought together in this single structure endow it with an extraordinary range of receptor and signaling functions. This organelle is based on the centriole, which is itself a minute compact structure that has been conserved throughout evolution for well over a billion years. After more than a century of interest in the presence and structural features of the primary cilium, it became clear from the advent of the electron microscope that they were much more ubiquitous and had many more functions in situations other than the most obvious of cases, that is, the retinal rods and cones. However, these other functional activities were considered to be largely speculative by nonspecialists, until more recently. In the last decade, more has been learned about their molecular biology and function than in all the preceding years of research. The impetus came from a better understanding of the process of ciliogenesis at the macromolecular level, the discovery of wide range of receptors localized in the ciliary membrane, and the appropriate signaling mechanisms to relay messages to the cell internum. These are the three central themes of current investigations. The reason for the recent flurry of activity stemmed from work in the mid-1990s emphasizing the fact that the failure of cells to develop primary cilia in certain tissues and organs was directly correlated with some drastic pathological consequences, just as failure to develop the primary cilia that form the basis of retinal cells, observed now over a half a century ago by Sjöstrand, F. S. (Sjöstrand, F. S. (1953). The ultrastructure of the inner segments of the retinal rods of the guinea pig eye as revealed by electron microscopy long ago, so blatantly causes blindness. The medical implications did in due course prove to be of such magnitude that highly intensive work began on primary cilia in the late 1990s and has since shown their involvement in a wide range of both serious and highly prevalent disorders. Since we are referring to an organelle that is made by and comprised of a whole host of nanomachines, it has become an obvious focus of attention in both academic and applied research. These rapid developments have relied on experts from many different disciplines, including engineering and physics, to help solve some of the problems. This article introduces the primary cilium to scientists from this wide range of disciplines who are interested in nanoscience and to those in particular who see the advantages of looking at biological systems. There is little doubt that our knowledge at the supramolecular (nanoscale) level of the primary cilium will, in turn, help (bio)engineers, (bio)technologists, and others to design and build ever more exquisitely sensitive sensors that will be of immense value in future, especially in fields such as medicine. If any aphorism rings true in these circumstances, it is that "nature has already been there." On this account alone, the primary cilium should command much more of our attention.
Wheatley
Denys N
DN
BioMedES, Leggat House, Keithhall, Inverurie, Aberdeen, United Kingdom.
D001692:Biological Transport; D049109:Cell Proliferation; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D036103:Nanotechnology / Q000379:methods*