PMC:3882725 / 16519-18579 JSONTXT

{"project":"2_test","denotations":[{"id":"24239382-10099934-2045379","span":{"begin":182,"end":184},"obj":"10099934"},{"id":"24239382-11409409-2045380","span":{"begin":319,"end":321},"obj":"11409409"},{"id":"24239382-20832290-2045381","span":{"begin":663,"end":665},"obj":"20832290"},{"id":"24239382-20965607-2045381","span":{"begin":663,"end":665},"obj":"20965607"},{"id":"24239382-21068295-2045381","span":{"begin":663,"end":665},"obj":"21068295"},{"id":"24239382-12684051-2045382","span":{"begin":1160,"end":1162},"obj":"12684051"},{"id":"24239382-20159109-2045383","span":{"begin":1412,"end":1414},"obj":"20159109"},{"id":"24239382-19377476-2045383","span":{"begin":1412,"end":1414},"obj":"19377476"},{"id":"24239382-11075828-2045384","span":{"begin":1705,"end":1707},"obj":"11075828"},{"id":"24239382-18374170-2045384","span":{"begin":1705,"end":1707},"obj":"18374170"},{"id":"24239382-21080001-2045384","span":{"begin":1705,"end":1707},"obj":"21080001"},{"id":"24239382-23769912-2045384","span":{"begin":1705,"end":1707},"obj":"23769912"},{"id":"24239382-12878700-2045385","span":{"begin":1854,"end":1856},"obj":"12878700"},{"id":"24239382-16361095-2045385","span":{"begin":1854,"end":1856},"obj":"16361095"},{"id":"24239382-18829961-2045385","span":{"begin":1854,"end":1856},"obj":"18829961"},{"id":"24239382-17476322-2045386","span":{"begin":2058,"end":2060},"obj":"17476322"},{"id":"24239382-17956734-2045386","span":{"begin":2058,"end":2060},"obj":"17956734"},{"id":"24239382-16361095-2045386","span":{"begin":2058,"end":2060},"obj":"16361095"},{"id":"24239382-17215396-2045386","span":{"begin":2058,"end":2060},"obj":"17215396"},{"id":"24239382-18430734-2045386","span":{"begin":2058,"end":2060},"obj":"18430734"},{"id":"24239382-21252856-2045386","span":{"begin":2058,"end":2060},"obj":"21252856"},{"id":"24239382-23554489-2045386","span":{"begin":2058,"end":2060},"obj":"23554489"},{"id":"24239382-11018051-2045386","span":{"begin":2058,"end":2060},"obj":"11018051"},{"id":"24239382-15169891-2045386","span":{"begin":2058,"end":2060},"obj":"15169891"},{"id":"24239382-22467854-2045386","span":{"begin":2058,"end":2060},"obj":"22467854"},{"id":"24239382-12389031-2045386","span":{"begin":2058,"end":2060},"obj":"12389031"},{"id":"24239382-20798032-2045386","span":{"begin":2058,"end":2060},"obj":"20798032"},{"id":"24239382-19859546-2045386","span":{"begin":2058,"end":2060},"obj":"19859546"}],"text":"Kaptin is a largely uncharacterized protein originally isolated from human blood platelets but subsequently found to be expressed in fibroblasts and intestinal and sensory epithelia.14 A previous study of this molecule suggested a role at stereocilia tips, and so KPTN was proposed as a candidate gene for hearing loss.15 However, the affected individuals described in this study have no evidence of sensorineural hearing deficits. During development, the actin cytoskeleton plays a pivotal role in neuronal cell morphology and migration, including the generation, protrusion, and steering of growth cones and the formation of postsynapse and dendritic spines.16–18 Our studies confirm kaptin expression in neuronal (MAP2-positive) cells. Given that kaptin was found to localize to F-actin-rich structures, it is conceivable that loss of kaptin function could either directly or indirectly lead to impairment of the neuronal actin cytoskeleton, required for dendritic arborization and/or spine formation, and result in the disease phenotype described. Support for this has been provided by studies of Rab39B, a small GTPase associated with the Golgi apparatus;19 alterations in this protein lead to its downregulation and a concomitant reduction in dendritic arborization and synapse formation. This was previously associated with a disease phenotype comprising mental retardation, epilepsy, and macrocephaly,20,21 features which overlap with those described here as arising from kaptin alterations. Similarly, deficiencies of Rho GTPases, which regulate the actin cytoskeleton by a growing variety of effector proteins, have been associated with intellectual disability and defects in spine structure.22–25 Several other actin-associated proteins, including drebrin A, cortactin, and Abp1, have also been found to decrease spine density or formation,26–28 and a growing body of evidence supports a role for the Arp2/3 complex and directly and indirectly associated proteins in postsynapse formation and proper development of neuronal morphology.10,11,27,29–38"}