MYOT
Encyclopedia
Myotilin is a protein
that in humans is encoded by the MYOT gene
.
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. 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, Filamin C, FATZ-1 and ZASP.
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. On the other hand, transgenic mice with mutated myotilin develop muscle dystrophy.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the MYOT gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
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. The C2-type Ig-like domains reside at the C-terminal half, and are most homologous to Ig domains 2-3 of palladin
Palladin
Palladin is a protein that in humans is encoded by the PALLD gene. Palladin is a component of actin-containing microfilaments that control cell shape, adhesion, and contraction.- Discovery :...
and Ig domains 4-5 of myopalladin and more distantly related to Z-disc Ig domains 7 and 8 of titin
Titin
Titin , also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured...
. 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, Filamin C, FATZ-1 and ZASP.
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
Titin
Titin , also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured...
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. On the other hand, transgenic mice with mutated myotilin develop muscle dystrophy.