Available structures
PDB Ortholog search: RCSB
RNA expression pattern

Myotilin is a protein that in humans is encoded by the MYOT gene.[1][2][3]

Striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin (TTN; MIM 188840), a giant molecule that contains several immunoglobulin (Ig)-like domains and associates with thin and thick filaments, and alpha-actinin (ACTN1; MIM 102575), an actin cross-linking protein. Mutations in several sarcomeric and sarcolemmal proteins have been shown to result in muscular dystrophy and cardiomyopathy.[supplied by OMIM][3]
Myotilin (myofibrillar titin-like protein) also known as TTID (TiTin Immunoglobulin Domain) is a skeletal muscle protein that is found within the Z-disc of sarcomeres. It is mutated in various forms of muscular dystrophy:

- Limb-Girdle Muscular Dystrophy type 1A (LGMD1A)
- Myofibrillar Myopathy (MFM)
- Spheroid Body Myopathy
- Distal Myopathy

Myotilin was originally identified as a novel alpha-actinin binding partner with two Ig-like domains, that localised to the Z-disc.[4] The C2-type Ig-like domains reside at the C-terminal half, and are most homologous to Ig domains 2-3 of palladin and Ig domains 4-5 of myopalladin and more distantly related to Z-disc Ig domains 7 and 8 of titin. By contrast, the N-terminal part of myotilin is unique, consisting of a serine-rich region with no homology to known proteins. Several disease-associated mutations involve serine residues within the serine-rich domain. Myotilin expression in human tissues is mainly restricted to striated muscles and nerves. In muscles, myotilin is predominantly found within the Z-discs. Myotilin forms homodimers and binds alpha-actinin, actin,[5] Filamin C,[6] FATZ-1[7] and ZASP.[8] Myotilin induces the formation of actin bundles in vitro and in non-muscle cells. A ternary complex myotilin/actin/alpha-actinin can be observed in vitro and actin bundles formed in this conditions appear more tightly packed than those induced by alpha-actinin alone. It was demonstrated that myotilin stabilises F-actin by slowing down the disassembly rate. Ectopic overexpression of truncated myotilin causes the disruption of nascent myofibrils and the co-accumulation of myotilin and titin in amorphous cytoplasmic precipitates. In mature sarcomeres, wild-type myotilin co-localises with alpha-actinin and Z-disc titin, showing the striated pattern typical of sarcomeric proteins. Targeted disruption of myotilin gene in mice does not cause significant alteration in muscle function.[9] On the other hand, transgenic mice with mutated myotilin develop muscle dystrophy.[10]


External links

  • GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy

Further reading

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