Molecular structure of cilia, a. Electron micrograph of longitudinally sectioned cilia from the oviduct. The internal structures within the ciliary process are microtubules. Most of the basal bodies appear "empty" because of the absence of the central pair of microtubules in this portion of the ciiium. One basal body (secondfrom left) has been sectioned peripherally through the outer microtubule triplet, x20,000. b. Schematic diagram of ciiium, showing its cross section (upper plane) with the pair of central microtubules and the nine surrounding microtubule doublets. The dynein arms extend from the A microtubule and make temporary cross-bridges with the B microtubule of the adjacent doublet. Inset. Compare the diagram with the cross section in the electron micrograph (c) and identify corresponding structures, x 180,000. The molecular structure of the microtubule doublet is shown adjacent to the cross section. Note that the A microtubule of the doublet is composed of 13 tubulin dimers arranged in a side-by-side configuration, whereas the B microtubule is composed of 10 tubulin dimers and shares the remaining dimers with those of the A microtubule. The cross section of the basal body (lower plane) shows the arrangement of nine microtubule triplets. These structures form a ring structure. Each microtubule doublet of the ciiium is an extension of two inner microtubules of the corresponding triplet.

tubulin subunits microtubule triplets central sheath projections central pair of microtubules microtubule doublets nexin-linking cross-bridges with the B microtubule of the adjacent doublet. A passive elastic component formed by nexin permanently links the A microtubule with the B microtubule of adjacent doublets at 86-nm intervals. The two central microtubules are separate but are partially enclosed by a central sheath projection at 14-nm intervals along the length of the cilium. Radial spokes extend from each of the nine doublets toward the two central microtubules at 29-nm intervals. The proteins forming the radial spokes and the nexin connections between the outer doublets make large-amplitude oscillations of the cilia possible.

The 9 + 2 microtubule array courses from the tip of the cilium to its base, where the outer paired microtubules join the basal body. The basal body is a modified centriole consisting of nine short microtubule triplets arranged in a ring. Each of the paired microtubules of the cilium is continuous with two of the triplet microtubules of the basal body. The two central microtubules of the cilium end at the level of the top of the basal body. Therefore, a cross section of the basal body would reveal nine circularly arranged microtubule triplets but not the two central single microtubules of the cilium.

Cilia develop from procentrioles

The process of ciliary formation in differentiating cells involves the replication of the centriole to give rise to multiple procentrioles, one for each cilium. The procentrioles grow and migrate to the apical surface of the cell, where each becomes a basal body. From each of the nine triplets that make up the basal body, a microtubule doublet grows upward, creating a projection of the apical membrane containing the nine doublets found in the mature cilium. Simultaneously, the two single central microtubules form within the ring of doublet microtubules, thus yielding the characteristic 9 + 2 arrangement.

Cilia beat in a synchronous pattern

Cilia display a regular and synchronous undulating movement. A cilium remains rigid as it exhibits a rapid forward movement called the effective stroke; it becomes flexible and bends on the slower return movement, the recovery stroke. The plane of movement of a cilium is perpendicular to a line joining the central pair of microtubules. Cilia in successive rows start their beat so that each row is slightly more advanced in its cycle than the following row, thus creating a wave that sweeps across the epithelium. This metachronal rhythm is responsible for moving mucus over epithelial surfaces or facilitating the flow of fluid and other substances through tubular organs and ducts.

Ciliary activity is based on the movement of the doublet microtubules in relation to one another. Ciliary movement is initiated by the dynein arms (see Fig. 4.6b). The ciliary dynein located in the arms of the A microtubule forms temporary cross-bridges with the B microtubule of the adjacent doublet. Hydrolysis of ATP produces a sliding movement of the bridge along the B microtubule. The dynein molecules produce a continuous

Cilia play a significant role in the human body. The mucociliary transport that occurs in the respiratory epithelium is one of the important mechanisms protecting the body against invading bacteria and other pathogens. Failure of the mucociliary transport system is caused by several hereditary disorders grouped under the general name of immotile cilia syndrome. Kartagener's syndrome, for instance, is caused by a structural abnormality involving absence of dynein arms (see electron micrograph at right). Young's syndrome is characterized by malformation of the radial spokes and the dynein arms. The most prominent symptom of immotile cilia syndrome is chronic respiratory difficulty (including bronchitis and sinusitis), although situs inversus of the viscera is also common. Respiratory problems are caused by severely impaired or absent ciliary motility that results in reduced or absent mucociliary transport in the tracheobronchial tree. The transposition of the viscera may be related to the lack of ciliary activity during the developmental process. Another possibility is that microtubules that designate a form of polarity within cells may also indirectly influence the polarity of organ systems. It may also result from abnormal microtubular

structure. Males with Kartagener's syndrome are sterile. The flagel-lum of the sperm, which is similar in structure to the cilium, is immotile. In contrast, some females with the syndrome may be fertile. In such individuals, the ciliary movement may be sufficient, though impaired, to permit transport of the ovum through the oviduct. (Photomicrograph courtesy of Patrice Abell-Aleff. x 180,000.)

shear force during this interdoublet sliding directed toward the ciliary tip. As a result of this ATP-dependent phase of the effective stroke, the cilium bends. At the same time, the passive elastic connections provided by nexin and the radial spokes accumulate the energy necessary to bring the cilium back to the straight position, thus producing the recovery stroke.

However, if all dynein arms along the length of the A microtubules in all nine doublets attempted to form temporary cross-bridges simultaneously, no effective stroke of the cilium would result. Thus, regulation of the active shear force is required. Current evidence suggests that the central pair of microtubules undergo rotation with respect to the nine outer doublets. This rotation may be driven by another motor protein, kinesin, which is associated with the central pair of microtubules. The central microtubule pair can act as a "distributor" that regulates the sequence of interactions of the dynein arms in a progressive manner to produce the effective stroke.

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