title: Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues.
abstract: Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors. The TSC2 tumor suppressor gene was recently identified by positional cloning and its protein product, tuberin, shown to represent one member of the rap GTPase activating protein (rapGAP) family. In order to determine the contribution of tuberin to the development of mental retardation and seizures in patients with TS, we examined the expression of tuberin in adult and developing nervous system tissues. Since tuberin is the second rapGAP found in the nervous system, the expression of tuberin was compared to the expression of rapGAP, rap1, and rap2. In this study, we demonstrate that tuberin is expressed at greatest levels in the spinal cord and cerebellum as opposed to rapGAP, which is not enriched in these tissues. Tuberin expression in the adult CNS is restricted to the olfactory bulb, several CNS neuronal populations, brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral spinal cord. In contrast, rapGAP is expressed in many different cell types in the adult CNS, but not in cerebellar Purkinje cells or motor neurons in the ventral spinal cord. However, there is significant expression of rapGAP in astrocytes. The restricted distribution of tuberin expression relative to rap1 and rapGAP suggests that tuberin may be the primary rap1 regulator in a subpopulation of CNS neurons.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Geist
authors.forename: A J
authors.initials: AJ
authors.lastname: Reddy
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009830:Olfactory Bulb / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020668:rap GTP-Binding Proteins
chemical_list: D005326:Fetal Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624654:Tsc2 protein, mouse; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins