title: Identification and functional analysis of a new putative caveolin-3 variant found in a patient with sudden unexplained death.
abstract: BACKGROUND
  Sudden cardiac death (SCD) is the clinical outcome of a lethal arrhythmia that can develop on the background of unrecognized channelopathies or cardiomyopathies. Several susceptibility genes have been identified for the congenital forms of these cardiac diseases, including caveolin-3 (Cav-3) gene. In the heart Cav-3 is the main component of caveolae, plasma membrane domains that regulate multiple cellular processes highly relevant for cardiac excitability, such as trafficking, calcium homeostasis, signal transduction and cellular response to injury. Here we characterized a new putative Cav-3 variant, Cav-3 V82I, found in a patient with SCD.
  
  
  RESULTS
  In heterologous systems Cav-3 V82I was expressed at significantly higher level than Cav-3 WT and accumulated within the cells. Cells expressing Cav-3 V82I exhibited a decreased activation of extracellular-signal-regulated kinases (ERKs) and were more vulnerable to sub-lethal osmotic stress.
  
  
  CONCLUSIONS
  Considering that abnormal loss of myocytes can play a mechanistic role in lethal cardiac diseases, we suggest that the detrimental effect of Cav-3 V82I variant on cell viability may participate in determining the susceptibility to cardiac death.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lariccia
authors.forename: Annamaria Assunta
authors.initials: AA
authors.lastname: Nasti
authors.forename: Federica
authors.initials: F
authors.lastname: Alessandrini
authors.forename: Mauro
authors.initials: M
authors.lastname: Pesaresi
authors.forename: Santo
authors.initials: S
authors.lastname: Gratteri
authors.forename: Adriano
authors.initials: A
authors.lastname: Tagliabracci
authors.affiliation: Department of Biomedical Sciences and Public Health, School of Medicine, University "Politecnica delle Marche", Ancona, Italy. s.amoroso@univpm.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Amoroso
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003645:Death, Sudden; D004789:Enzyme Activation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology
chemical_list: C417736:CAV3 protein, human; D051244:Caveolin 3; D048049:Extracellular Signal-Regulated MAP Kinases