Myopodin
protein, also called Synaptopodin-2 is a
protein that in humans is encoded by the ''SYNPO2''
gene.
Myopodin is expressed in
cardiac,
smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
and
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
, and localizes to
Z-disc structures.
Structure
Myopodin is a 117.4 kDa protein composed of 1093 amino acids, although four alternatively-spliced isoforms have been described. Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential
nuclear localization sequence A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines o ...
s (one
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
and one
C-terminal).
PPXY motifs have been shown to mediate
interactions
Interaction is action that occurs between two or more objects, with broad use in philosophy and the sciences. It may refer to:
Science
* Interaction hypothesis, a theory of second language acquisition
* Interaction (statistics)
* Interactions o ...
, and PXXP motifs represent potential sites of
interaction for
SH3 domain-containing proteins. Myopodin contains a novel
actin binding site (between amino acids 410 and 563) in the center of the protein.
Function
During
myotube
Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development.
Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development ...
differentiation, myopodin
interacts with
stress fibers prior to co-localizing with
alpha actinin-2 at
Z-discs in mature striated muscle cells.
Myopodin has been shown to shuttle between the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
and
cytoplasm in
myoblasts and myotubes in response to stress; its export from the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
is sensitive to
lemtomycin B.
The nuclear localization of myopodin is sensitive to
Importin 13, which directly binds myopodin and facilitates its translocation.
Importin binding and nuclear import of myopodin appears to be mediated by
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 ...
/
threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COOâ ...
phosphorylation-dependent binding of myopodin to
14-3-3 beta
14-3-3 protein beta/alpha is a protein that in humans is encoded by the ''YWHAB'' gene.
Function
This gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-co ...
Myopodin appears to regulate compartmentalized, intracellular signal transduction between the
Z-disc and
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
in
cardiac muscle cells, by forming a
Z-disc signaling complex with
alpha actinin-2,
calcineurin,
CaMKII,
muscle-specific A-kinase anchoring protein, and
myomegalin
Myomegalin, also known as phosphodiesterase 4D-interacting protein or cardiomyopathy-associated protein 2, is a protein that in humans is encoded by the ''PDE4DIP'' gene. It has roles in the formation of microtubules from the centrosome. Its name ...
.
Specifically, phosphorylation by
protein kinase A or
CaMKII, and dephosphorylation by
calcineurin facilitates the binding or release, respectively, of
14-3-3-beta, and the corresponding
nuclear
Nuclear may refer to:
Physics
Relating to the nucleus of the atom:
* Nuclear engineering
*Nuclear physics
*Nuclear power
*Nuclear reactor
*Nuclear weapon
*Nuclear medicine
*Radiation therapy
*Nuclear warfare
Mathematics
*Nuclear space
*Nuclear ...
or
cytoplasmic localization, respectively, of myopodin.
Interactions
Myopodin
interacts with:
*
14-3-3 beta
14-3-3 protein beta/alpha is a protein that in humans is encoded by the ''YWHAB'' gene.
Function
This gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-co ...
,
*
Actin, alpha, cardiac muscle 1,
*
Actinin, alpha 2,
*
Calcineurin,
*
CaMKII,
*
Importin 13,
and
*
Protein kinase A.
References
Further reading
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