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Acrosome
A c ro s o m e 3 high cervical myelopathy, central apnea, or profound hypotonia and motor delay and may, in some instances, require decompressive neurosurgery. Other potential complications in infancy include significant nasal obstruction that may lead to sleep apnea in a minority (5%) of cases, development of a thoracolumbar kyphosis, which usually resolves upon weight-bearing, and hydrocephalus in a small proportion of cases (1%) during the first 2 years of life, which may require shunting. From early childhood, and as the child begins to walk, several orthopedic manifestations may evolve including progressive bowing of the legs due to fibular overgrowth, development of lumbar lordosis, and hip flexion contractures. Recurrent ear infections with ensuing chronic serous otitis media are common complications at this time and may lead to conductive hearing loss with consequent delayed speech and language development. The older child with achondroplasia commonly develops dental malocclusion secondary to a disproportionate cranial base with subsequent crowding of teeth and crossbite. The main potential medical complication of the adult with achondroplasia is lumbar spinal canal stenosis, with impingement on the spinal cord roots. This complication may be manifested by lower limb pain and parasthesiae, bladder or bowel dysfunction, and neurological signs and may require decompressive surgery. Throughout their lives, some people with achondroplasia may experience a variety of psychosocial challenges. These can be addressed by specialized medical and social support of the individual and family, appropriate anticipatory guidance and by interaction with patient support groups such as the ``Little People of America.'' See also: Genetic Diseases
Acquired Resistance See: Systemic Acquired Resistance (SAR)
Acridines J H Miller Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0003
A group of polycyclic hydrocarbons, often used as dyes, that intercalate into the DNA, often resulting in the insertion or deletion of base pairs, generating frameshift mutations.
Acrocentric Chromosome Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1751
An acrocentric chromosome possesses a centromere nearer to one end than the other. See also: Centromere; Chromosome
Acrosome G S Kopf Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0004
The acrosome is a vesicle overlying the nucleus of both invertebrate and vertebrate sperm composed of nonenzymatic and enzymatic proteins generally arranged as a matrix; these proteins have been demonstrated in some cases to play specific roles in the fertilization process. The contents of the acrosome are released prior to sperm±egg fusion in a regulated secretory event called the acrosome reaction. The morphology of the acrosome varies between species and the mechanics of the acrosome reaction vary widely between invertebrates and vertebrates. This chapter will focusspecificallyontheacrosomeofmammaliansperm. The acrosome is a product of the Golgi complex, and is synthesized and assembled during spermiogenesis. The contents of the acrosome include structural and nonstructural, nonenzymatic and enzymatic components, and this secretory vesicle is delimited by both inner and outer acrosomal membranes. These components appear to play important roles in the establishment and maintenance of the acrosomal matrix, in the dispersion of the acrosomal matrix, in the penetration of the egg's zona pellucida, and possibly in the interaction between the sperm and the egg plasma membranes. This vesicle is finally confined within the plasma membrane overlying the entire sperm surface. There remain several questions pertaining to the formation and maturation of this organelle. For example, although prominent biogenesis of the acrosome occurs during the Golgi and cap phases of spermiogenesis, it is not clear when it is during this developmental process that this organelle actually starts to develop. Furthermore, the acrosome is composed of multiple component proteins, but little is known regarding whether the synthesis of all of these components occurs at the same time or whether synthesis is ordered and coordinate. Experimental evidence to date suggests the latter mechanism.
4
Active S ite
The mechanisms by which these acrosomal components are targeted to this organelle during biogenesis are also not known. Although spermatogenic cells possess functional mannose-6-phosphate/insulin-like growth factor II receptors, it is not clear whether these receptors play a role in the transport of glycoproteins to the acrosome or whether targeting occurs primarily through the `default' pathway seen in the transport of proteins in other secretory systems. Finally, once these components are packaged into the acrosome, the functional significance of additional processing of these components (i.e., posttranslational modifications; movement within the organelle) during sperm residence in the testis and/or during residence in the extratesticular male reproductive organs (i.e., epididymis; vas deferens) is not clear. In some species (e.g., guinea pig, mouse), the formation of specific protein domains within the acrosome has been clearly demonstrated, but the mechanism by which this compartmentalization is established is poorly understood and an understanding of the biological role of this compartmentalization is only starting to be realized. Answers to all of these questions will no doubt become apparent when a systematic evaluation of the proteins comprising the acrosome is undertaken with respect to transcription, translation, and posttranslational modifications. An understanding of these processes may greatly further our knowledge of the role of the acrosome in fertilization since it is becoming apparent that this secretory vesicle may have multiple functions (see below). It should also be noted that individuals whose sperm have poorly formed acrosomes or lack acrosomes altogether display infertility; this speaks to the importance of this organelle in the normal fertilization process. In any event, studies focused on the synthesis and processing of acrosomal components should be considered in the context of the acrosome functioning as a secretory granule and not a modified lysosome, as has been historically suggested. Although the fusion of the plasma membrane overlying the acrosome and the outer acrosomal membrane constitutes the acrosome reaction, it must be emphasized that this process is very complex and likely involves many of the steps constituting regulated exocytotic processes in other cell types. Such steps might include membrane priming, docking, and fusion. Therefore, this process can also be referred to as acrosomal exocytosis. Recent data support the idea that sperm capacitation, an extratesticular maturational process that normally occurs in the female reproductive tract and confers fertilization competence to the sperm, may comprise signal transduction events that ready the plasma and outer acrosomal membranes for subsequent fusion during the process of acrosomal exocytosis. Acrosomal exocytosis is
regulated by ligand-induced signal transduction events in which the physiologically relevant ligand is the zona pellucida, an oocyte-specific extracellular matrix. Specific components of the zona pellucida are responsible for species-specific binding of the sperm and subsequent acrosomal exocytosis. These events are likely mediated by sperm membrane-associated zona pellucida binding proteins and/or receptors; the identity and mode of action of such proteins is still quite controversial. Resultant exocytosis involves the point fusion and vesiculation of the plasma membrane overlying the acrosome with the outer acrosomal membrane, thus creating hybrid membrane vesicles. The molecular mechanisms involved in this fusion and vesiculation process are not known. The resultant fusion of these membranes leads to the subsequent exposure of the acrosomal contents to the extracellular environment. Both the exposed soluble and insoluble components of the acrosome may play important roles in the binding of the acrosome reacted sperm to the zona pellucida, as well as the subsequent penetration of the acrosome reacted sperm through the zona pellucida. Although this exocytotic event can be induced by both physiological stimuli and pharmacological agents, the molecular mechanisms by which these different stimuli and agents function to induce exocytosis may be dramatically different. See also: Fertilization
Active Site Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1752
An active site is the part or region of a protein to which a substrate binds. See also: Proteins and Protein Structure
Adaptive Landscapes M B Cruzan Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0006
Overview The genetic determination of fitness is complex, involving a large number of loci with numerous interactions. In 1932 Sewall Wright depicted this myriad of effects as a two-dimensional view of peaks and valleys that represented fitness levels of multilocus genotypes
Acquired Resistance See: Systemic Acquired Resistance (SAR)
Acridines J H Miller Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0003
A group of polycyclic hydrocarbons, often used as dyes, that intercalate into the DNA, often resulting in the insertion or deletion of base pairs, generating frameshift mutations.
Acrocentric Chromosome Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1751
An acrocentric chromosome possesses a centromere nearer to one end than the other. See also: Centromere; Chromosome
Acrosome G S Kopf Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0004
The acrosome is a vesicle overlying the nucleus of both invertebrate and vertebrate sperm composed of nonenzymatic and enzymatic proteins generally arranged as a matrix; these proteins have been demonstrated in some cases to play specific roles in the fertilization process. The contents of the acrosome are released prior to sperm±egg fusion in a regulated secretory event called the acrosome reaction. The morphology of the acrosome varies between species and the mechanics of the acrosome reaction vary widely between invertebrates and vertebrates. This chapter will focusspecificallyontheacrosomeofmammaliansperm. The acrosome is a product of the Golgi complex, and is synthesized and assembled during spermiogenesis. The contents of the acrosome include structural and nonstructural, nonenzymatic and enzymatic components, and this secretory vesicle is delimited by both inner and outer acrosomal membranes. These components appear to play important roles in the establishment and maintenance of the acrosomal matrix, in the dispersion of the acrosomal matrix, in the penetration of the egg's zona pellucida, and possibly in the interaction between the sperm and the egg plasma membranes. This vesicle is finally confined within the plasma membrane overlying the entire sperm surface. There remain several questions pertaining to the formation and maturation of this organelle. For example, although prominent biogenesis of the acrosome occurs during the Golgi and cap phases of spermiogenesis, it is not clear when it is during this developmental process that this organelle actually starts to develop. Furthermore, the acrosome is composed of multiple component proteins, but little is known regarding whether the synthesis of all of these components occurs at the same time or whether synthesis is ordered and coordinate. Experimental evidence to date suggests the latter mechanism.
4
Active S ite
The mechanisms by which these acrosomal components are targeted to this organelle during biogenesis are also not known. Although spermatogenic cells possess functional mannose-6-phosphate/insulin-like growth factor II receptors, it is not clear whether these receptors play a role in the transport of glycoproteins to the acrosome or whether targeting occurs primarily through the `default' pathway seen in the transport of proteins in other secretory systems. Finally, once these components are packaged into the acrosome, the functional significance of additional processing of these components (i.e., posttranslational modifications; movement within the organelle) during sperm residence in the testis and/or during residence in the extratesticular male reproductive organs (i.e., epididymis; vas deferens) is not clear. In some species (e.g., guinea pig, mouse), the formation of specific protein domains within the acrosome has been clearly demonstrated, but the mechanism by which this compartmentalization is established is poorly understood and an understanding of the biological role of this compartmentalization is only starting to be realized. Answers to all of these questions will no doubt become apparent when a systematic evaluation of the proteins comprising the acrosome is undertaken with respect to transcription, translation, and posttranslational modifications. An understanding of these processes may greatly further our knowledge of the role of the acrosome in fertilization since it is becoming apparent that this secretory vesicle may have multiple functions (see below). It should also be noted that individuals whose sperm have poorly formed acrosomes or lack acrosomes altogether display infertility; this speaks to the importance of this organelle in the normal fertilization process. In any event, studies focused on the synthesis and processing of acrosomal components should be considered in the context of the acrosome functioning as a secretory granule and not a modified lysosome, as has been historically suggested. Although the fusion of the plasma membrane overlying the acrosome and the outer acrosomal membrane constitutes the acrosome reaction, it must be emphasized that this process is very complex and likely involves many of the steps constituting regulated exocytotic processes in other cell types. Such steps might include membrane priming, docking, and fusion. Therefore, this process can also be referred to as acrosomal exocytosis. Recent data support the idea that sperm capacitation, an extratesticular maturational process that normally occurs in the female reproductive tract and confers fertilization competence to the sperm, may comprise signal transduction events that ready the plasma and outer acrosomal membranes for subsequent fusion during the process of acrosomal exocytosis. Acrosomal exocytosis is
regulated by ligand-induced signal transduction events in which the physiologically relevant ligand is the zona pellucida, an oocyte-specific extracellular matrix. Specific components of the zona pellucida are responsible for species-specific binding of the sperm and subsequent acrosomal exocytosis. These events are likely mediated by sperm membrane-associated zona pellucida binding proteins and/or receptors; the identity and mode of action of such proteins is still quite controversial. Resultant exocytosis involves the point fusion and vesiculation of the plasma membrane overlying the acrosome with the outer acrosomal membrane, thus creating hybrid membrane vesicles. The molecular mechanisms involved in this fusion and vesiculation process are not known. The resultant fusion of these membranes leads to the subsequent exposure of the acrosomal contents to the extracellular environment. Both the exposed soluble and insoluble components of the acrosome may play important roles in the binding of the acrosome reacted sperm to the zona pellucida, as well as the subsequent penetration of the acrosome reacted sperm through the zona pellucida. Although this exocytotic event can be induced by both physiological stimuli and pharmacological agents, the molecular mechanisms by which these different stimuli and agents function to induce exocytosis may be dramatically different. See also: Fertilization
Active Site Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1752
An active site is the part or region of a protein to which a substrate binds. See also: Proteins and Protein Structure
Adaptive Landscapes M B Cruzan Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0006
Overview The genetic determination of fitness is complex, involving a large number of loci with numerous interactions. In 1932 Sewall Wright depicted this myriad of effects as a two-dimensional view of peaks and valleys that represented fitness levels of multilocus genotypes