Multiple effects of sarco/endoplasmic reticulum Ca2+-ATPase mutations associated with Darier's disease on cellular calcium signaling
Year: 2003
Type: dissertation
Abstract: Darier's disease (DD) is an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization.Recently, mutations in the ATP2A2 gene encoding a Ca 2+ -ATPase pump of the sarco/endoplasmic reticulum (SERCA2) have been discovered as the cause of DD.In the present work twelve DDcausing SERCA2b mutations were selected to study the underlying pathologic mechanisms of DD and to elucidate the role of SERCA2b in calcium signaling.Most mutations markedly affected protein expression, partially due to enhanced proteasome-mediated degradation.When SERCA activity was measured in mutant-transfected cells, all DD-causing mutants showed lower activity than the wild type SERCA2b.Several mutants that cause relatively severe phenotype of DD inhibited endogenous and the cotransfected wild type SERCA2b activity.These effects were not due to changes in passive leak, IP 3 receptor activity or sensitivity to IP 3 .In co-immunoprecipitation experiments, SERCA2b monomers interact to influence the activity of each other.These findings reveal the importance of SERCA2b dimerization and ER Ca 2+ in physiologic cellular function and pathogenesis of DD.
Author: 안우인
Language: English
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2418440668