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 muscle protein that is found within the
Z-disc of
sarcomeres.
Structure
Myotilin is a 55.3 kDa protein composed of 496 amino acids.
Myotilin was originally identified as a novel
alpha-actinin binding partner with two
Ig-like domains, that localized to the
Z-disc. The I-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. The C-terminal region hosts the binding sites for Z-band proteins, and 2
Ig domains are the site of homodimerization for myotilin.
By contrast, the N-terminal part of myotilin is unique, consisting of a
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
-rich region with no homology to known proteins. Several disease-associated mutations involve
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
residues within the
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
-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,
FATZ-2 and
ZASP.
Function
Myotilin is a structural protein that, along with
titin and
alpha-actinin give structural integrity to
sarcomeres at
Z-discs in striated muscle. 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 under these conditions appear more tightly packed than those induced by
alpha-actinin alone. It was demonstrated that myotilin stabilizes
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 colocalizes with
alpha-actinin and
Z-disc titin, showing the striated pattern typical of
sarcomeric proteins. Targeted disruption of the myotilin gene in mice does not cause significant alterations in muscle function. On the other hand, transgenic mice with mutated myotilin develop muscle dystrophy.
Clinical significance
Myotilin is mutated in various forms of muscular dystrophy: Limb-Girdle Muscular Dystrophy type 1A (LGMD1A), Myofibrillar Myopathy (MFM), Spheroid Body Myopathy and Distal Myopath.
The mechanism underlying the pathology is still under investigation. It has been shown that actin binding properties of myotilin housing pathogenic mutations (
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
55
Phe,
Thr57
Ile
Ile may refer to:
* iLe, a Puerto Rican singer
* Ile District (disambiguation), multiple places
* Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria
* Interlingue (ISO 639:ile), a planned language
* Isoleucine, an amino acid
* Anothe ...
,
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
60
Cys, and
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
95
Ile
Ile may refer to:
* iLe, a Puerto Rican singer
* Ile District (disambiguation), multiple places
* Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria
* Interlingue (ISO 639:ile), a planned language
* Isoleucine, an amino acid
* Anothe ...
) are normal,
albeit with a slower rate of degradation.
Surprisingly, YFP-fusion constructs of myotilin mutants (
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
55
Phe,
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
55
Ile
Ile may refer to:
* iLe, a Puerto Rican singer
* Ile District (disambiguation), multiple places
* Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria
* Interlingue (ISO 639:ile), a planned language
* Isoleucine, an amino acid
* Anothe ...
,
Thr57
Ile
Ile may refer to:
* iLe, a Puerto Rican singer
* Ile District (disambiguation), multiple places
* Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria
* Interlingue (ISO 639:ile), a planned language
* Isoleucine, an amino acid
* Anothe ...
,
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
60
Cys,
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
60
Phe,
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
95
Ile
Ile may refer to:
* iLe, a Puerto Rican singer
* Ile District (disambiguation), multiple places
* Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria
* Interlingue (ISO 639:ile), a planned language
* Isoleucine, an amino acid
* Anothe ...
,
Arg
Arg or ARG may refer to:
Places
*''Arg'' () means "citadel" in Persian, and may refer to:
**Arg, Iran, a village in Fars Province, Iran
**Arg (Kabul), presidential palace in Kabul, Afghanistan
**Arg, South Khorasan, a village in South Khorasan P ...
405
Lys) localized normally to
Z-discs and exhibited normal dynamics in muscle cells.
References
Further reading
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External links
*
GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy*
{{Muscle tissue
Human proteins