TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance.
J Clin Invest
; 134(2)2024 Jan 16.
Article
em En
| MEDLINE
| ID: mdl-38226618
ABSTRACT
Titin (TTN) is one of the largest and most complex proteins expressed in humans, and truncation variants are the most prevalent genetic lesion identified in individuals with dilated cardiomyopathy (DCM) or other disorders of impaired cardiac contractility. Two reports in this issue of the JCI shed light on a potential mechanism involving truncated TTN sarcomere integration and the potential for disruption of sarcomere structural integrity. Kellermayer, Tordai, and colleagues confirmed the presence of truncated TTN protein in human DCM samples. McAfee and authors developed a patient-specific TTN antibody to study truncated TTN subcellular localization and to explore its functional consequences. A "poison peptide" mechanism emerges that inspires alternative therapeutic approaches while opening new lines for inquiry, such as the role of haploinsufficiency of full-length TTN protein, mechanisms explaining sarcomere dysfunction, and explanations for variable penetrance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcômeros
/
Cardiomiopatia Dilatada
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article