Fig 3-20 Association of kinesin motor protein to a microtubule and the limiting membrane of a cytoplasmic vesicle. Adenosine triphosphatase (ATP) activity in the globular head group of the motor microtubule-associate protein causes displacement of the vesicle toward the positive end of the microtubule.
Individual members of these two families of motor MAPs appear to be relegated to the movement of specific cytoplasmic organelles and inclusions, for example, secretory granules, mitochondria, and transport vesicles. Specificity is believed to be a function of the binding affinity of carboxy tail domains of the motor MAP to target (receptor) proteins in the membrane of the transported entity.
Microtubule-associated structural proteins (structural MAPs) help to stabilize MTs by forming bridges to other cytoplasmic proteins.156,161 They are present in high numbers in axons and dendrites of nerve cells. Approximately 15% to 20% of the total proteins of the brain are made of tubulin and MAPs.
Because of the abundance of structural MAPs in the brain, the neuronal MAPs have been most highly studied. Neuronal MAPs stabilize and promote the alignment of MTs in parallel arrays in axons and dendrites. In nonneuronal cells of the body, MTs are stabilized and bundled by MAP4. Phosphorylation of serine and threonine residues on MAPs by various kinases leads to MAP inactivation and decreased ability to interact with tubulin. On the other hand, the action of various phosphatases can activate MAPs and increase the organization of MT systems.
Enamel dysplasia
Alteration of the ionic and metabolic milieu of secretory and maturation ameloblasts leads to defective enamel (enamel dysplasia). Because enamel does not remodel, its defects are retained in the fully formed tooth. Interference with the secretion stage leads to a reduction in the amount and/or composition of the enamel matrix, a condition known as enamel hypoplasia. The resulting enamel is thinner than normal, but usually fully mineralized. If the interference affects maturation ameloblasts, the result will be hypomaturation and hypomineralization. The resulting enamel contains more protein than normal, and the hydroxyapatite crystallites fail to reach their normal size.
Early maturation appears to be a critical stage in the formation of sound enamel, because disturbances occurring during the period when transitional ameloblasts differentiate into maturation ameloblasts lead to prolonged periods of suboptimal mineralization.162 Differentiating and secretory ameloblasts appear to have a greater potential for recovering normal function following metabolic insult.
Enamel affected by hypomaturation is usually of full thickness but more porous and less mineralized. Because it is less translucent, hypomaturated enamel appears clinically as white spots, or it may appear stained because of the subsequent absorption of extraneous molecules derived from food and serum. Dysplastic enamel usually contains physical evidence that both matrix deposition and maturation have been altered. Such teeth may have horizontal rows of pits and grooves of discolored and white opaque enamel.
Enamel dysplasia can be caused by local, systemic, and hereditary factors:
1. Anoxia in premature birth
2. Congenital syphilis
3. Erythrobastosis fetalis
4. Exantematous infections
5. Fluorosis
6. Hypoparathyroidism
7. Hypothyroidism
8. Renal hypophosphatasia
9. Vitamin A deficiency
10. Vitamin D–resistant rickets
In locally acting etiologies, there is no regular pattern involving contralateral teeth and no consistent pattern with relation to timing. An example of a local factor is an inflammatory process in a carious primary tooth that affects the nearby dental germ of its permanent replacement.
In a patient with enamel defects, symmetry of the lesions usually indicates a systemic cause. Systemic agents act in a symmetric and contemporaneous manner to involve all teeth under development at the time of the insult. Based on the position, distribution, and nature of the lesions, the approximate time period over which a disease occurred can be determined. The chronology of enamel formation (Fig 3-21) reveals how a serious systemic disease, such as pneumonia or measles, affecting a 1-year-old child will cause enamel hypoplasia of the permanent incisors, canines, and first molars.163 A similar disease occurring in a 3-year-old child will affect the maturation phase in the incisors and canines and the secretory phase of the premolars. Recurrent systemic diseases, or the medications used in their treatment, frequently produce a series of symmetric horizontal ridges and grooves across the enamel surface.
Fig 3-21 Period of amelogenesis in the permanent teeth of the human dentition. Each bar represents the duration of enamel formation from beginning to completion of maturation. (Adapted from Seltzer and Bender.163)
Enamel defects caused by environmental factors are not uncommon. In a study of more than 1,500 schoolchildren in London, it was reported that 68% had enamel defects in the permanent dentition.164 More than 10% had defects on 10 teeth or more.
Genetically acquired enamel defects are much rarer than the environmentally produced varieties. Hereditary enamel dysplasia, also known as amelogenesis imperfecta, occurs in several forms. The hypoplastic form, involving the secretion stage, leads to thin enamel. The teeth are smaller and lack contact points. Exposure of dentin and hypersensitivity are common sequelae. In the hypocalcified or hypomatured type, the enamel is soft, deeply stained, and easily chipped away from the dentin. In general, affected enamel shows an inverse relationship between mineral and protein contents.165
Amelogenesis imperfecta may be inherited as an autosomal-dominant defect with variable penetrance or as a sex-linked dominant trait. It was recently shown that a mutation in the AMEX gene, deleting nine base pairs in exon 2, resulting in the loss of three amino acids and the exchange of one amino acid in the signal peptide of amelogenin, was sufficient to cause severe enamel hypoplasia (Fig 3-22).166 In yet another family, a mutation on the AMEX gene, leading to the deletion of a much larger segment (5 kilobases) and the loss of entire exons, caused hypomineralization of enamel (Figs 3-22 and 3-23).167
Fig 3-22 Base pair and amino acid sequences of normal and mutant signal peptide portions of the human AMEX gene and amelogenin protein. Mutation leading to the loss of a tripeptide (isoleucine, leucine, and phenylalanine) and the substitution of threonine for alanine cause severe hypoplasia. (Adapted from Lagerström-Fermér et al167 with permission.)
Fig 3-23 Two mutations on the AMEX gene that cause amelogenesis imperfecta. (Adapted from Lagerström-Fermér et al167 with permission.)
Enamel pits and fissures
During the development of multicusped teeth, pit and fissure defects are formed in the steep depressions separating adjacent cusps.