Group:MUZIC:Nebulin

Introduction

Nebulin (UniProt ID: P20929 [1]) is a very large filamentous protein (600-900 kDa) ^[1] tightly associated to the thin filament of the muscle sarcomere throughout its length. Nebulin is mostly found within the sarcomeres of skeletal muscles but was also identified at a low level in cardiac muscle cells ^[2]. However, the sarcomeres of cardiac muscles predominantly contain a Nebulin-like protein called Nebulette (UniProt ID: O76041 [2]) which is a "short version" of Nebulin (100 kDa), highly similar to its C-terminal part ^[3].

Function

The Nebulin protein is involved in the structural integrity of the sarcomeres and is linked to many signalling pathways crucial for the maintenance of the sarcomere. The main fucntions of Nebulin are ^[4]: 1. To define and regulate the length of the thin filaments of actin (molecular ruler); 2. To maintain the alignment of adjacent myofibrills (linker of adjacent Z-disks); 3. To regulate muscle contraction (regulator of cross-bridge cycles).

Mutations in the Nebulin encoding gene are the most common cause of Nemaline myopathy (NM), a non-dystrophic congenital muscle disorder characterised by muscle weakness.