Nx3 Is a Z-Disk Structural and Signaling Hub That Is Reduced in Heart Failure.

ABSTRACT:

Background

Nx3 (novex-3) is an exceptionally small isoform of the giant protein titin, whose structural and functional roles within the sarcomere remain poorly understood.

Methods

We used a comprehensive, multimodal approach to define the key properties of Nx3 in healthy and failing hearts, including its abundance relative to FLT (full-length titin), sarcomeric localization, protein interactions, and functional relevance in mouse and human cardiomyocytes under physiological and pathological conditions. Using Western blotting, quantitative polymerase chain reaction, total RNA sequencing, and ribosome profiling, we show that Nx3 is constitutively expressed from fetal development through adulthood.

Results

In adult mouse and human myocardium, Nx3 accounts for ≈20% to 25%

SUBMITTER: Linke WA 

PROVIDER: S-EPMC13649281 | biostudies-literature | 2026 Oct

REPOSITORIES: biostudies-literature