Group:MUZIC:Myopodin: Difference between revisions

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==Introduction==

The protein synaptopodin-2 (encoded by the gene SYNPO2[http://www.uniprot.org/uniprot/Q9UMS6]), also called "myopodin", genethonin-2, synaptopodin-like and fesselin, is together with synaptopodin and tritopodin/CHAP a member of the podin protein family. It is widely expressed in striated, heart and smooth muscle cells where it localizes to Z-disks and dense bodies, respectively <ref name="r1"> PMID:11673475 </ref>. Myopodin is a multiadapter protein that interacts with filamentous actin, α-actinin and filamin. Different isoforms result from alternative splicing and alternative promoter usage and the predicted size of the resulting proteins varies between 74 kDa and 136 kDa; these variants show differential tissue distribution. The discrepancy between calculated molecular mass and apparent mobility in SDS-PAGE is at present still unclear, but might be due to post-translational modifications <ref> PMID:20554076 </ref> <ref> PMID:18371299 </ref> <ref> PMID:11696420</ref> <ref> PMID:12917631 </ref> <ref> PMID:18588515 </ref>. The lower molecular mass myopodin isoforms are dual compartment proteins that redistribute between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced manner <ref> PMID:C2150840 </ref>. Although its biological function is still undefined, recent findings support a role for myopodin as a z-disc multiadaptor protein (96).

The protein synaptopodin-2 (encoded by the gene SYNPO2[http://www.uniprot.org/uniprot/Q9UMS6]), also called '''myopodin''', genethonin-2, synaptopodin-like and fesselin, is together with synaptopodin and tritopodin/CHAP a member of the podin protein family. It is widely expressed in striated, heart and smooth muscle cells where it localizes to Z-disks and dense bodies, respectively <ref name="r1"> PMID:11673475 </ref>. Myopodin is a multiadapter protein that interacts with filamentous actin, α-actinin and filamin. Different isoforms result from alternative splicing and alternative promoter usage and the predicted size of the resulting proteins varies between 74 kDa and 136 kDa; these variants show differential tissue distribution. The discrepancy between calculated molecular mass and apparent mobility in SDS-PAGE is at present still unclear, but might be due to post-translational modifications <ref> PMID:20554076 </ref> <ref> PMID:18371299 </ref> <ref> PMID:11696420</ref> <ref> PMID:12917631 </ref> <ref> PMID:18588515 </ref>. The lower molecular mass myopodin isoforms are dual compartment proteins that redistribute between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced manner <ref> PMID:C2150840 </ref>. Although its biological function is still undefined, recent findings support a role for myopodin as a z-disc multiadaptor protein (96).

==Sequence Annotation==

Myopodin contains one PPXY motif and multiple PXXP motifs <ref name="r1"> PMID:11673475 </ref>. Beside 2 lysine-rich NLS sites (consensus motif K-K/RX-K/R) myopodin provides 2 binding sites for 14-3-3(consensus motif a: RSXpS/TXP; b: RXXXpS/TXP Biophys Rev (2010) 2:181-189). These sites seem to be indispensable for effective shuttling of myopodin from the Z-disk into the nucleus <ref> PMCID:PMC2171942 </ref>. Phosphorylation of myopodin within the 14-3-3 binding sites (S225 and T272) by protein kinase A and ~~Ca2~~+/calmodulin-dependent protein kinase II abrogates the binding with α -actinin and promotes the binding with 14-3-3 and importin α <ref> PMID:17923693 </ref>. Another important domain present in myopodin is the PDZ domain (postsynaptic density 95, discs large, and zonula occludens-1). PDZ domains are protein-protein interaction modules that can mediate multiple biological processes such as vesicle transport, ion channel signaling, and signal transduction in several tissues. PDZ domains in myopodin are of unknown function <ref> PMID:18371299 </ref>.

Myopodin contains one PPXY motif and multiple PXXP motifs <ref name="r1"> PMID:11673475 </ref>. Beside 2 lysine-rich NLS sites (consensus motif K-K/RX-K/R) myopodin provides 2 binding sites for 14-3-3(consensus motif a: RSXpS/TXP; b: RXXXpS/TXP Biophys Rev (2010) 2:181-189). These sites seem to be indispensable for effective shuttling of myopodin from the Z-disk into the nucleus <ref> PMCID:PMC2171942 </ref>. Phosphorylation of myopodin within the 14-3-3 binding sites (S225 and T272) by protein kinase A and Ca<sup>2+</sup>/calmodulin-dependent protein kinase II abrogates the binding with α -actinin and promotes the binding with 14-3-3 and importin α <ref> PMID:17923693 </ref>. Another important domain present in myopodin is the PDZ domain (postsynaptic density 95, discs large, and zonula occludens-1). PDZ domains are protein-protein interaction modules that can mediate multiple biological processes such as vesicle transport, ion channel signaling, and signal transduction in several tissues. PDZ domains in myopodin are of unknown function <ref> PMID:18371299 </ref>.

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A filamin-binding region was mapped to a fragment encompassing amino acids 240–521 of myopodin, i.e. a region that contains two of the previously described homology regions shared by myopodin and synaptopodin <ref> PMID:20554076 </ref>.

Yeast two-hybrid analysis also identified an interaction of myopodin with zyxin, which leads to slower migration of prostate cancer cells and reduced invasiveness <ref> PMID:16885336 </ref>.

In cardiomyocytes, myopodin forms a Z-disc signaling complex with α-actinin, calcineurin, ~~Ca2~~+/calmodulin-dependent kinase II (CaMKII), muscle-specific A-kinase anchoring protein, and myomegalin. Calcineurin keeps myopodin dephosphorylated preventing 14-3-3ß binding to myopodin. Upon activation of PKA/CaMKII or inhibition of calcineurin, myopodin undergoes phosphorylation, enabling its interaction with 14-3-3ß, which releases myopodin from the Z-disc-anchoring proteins and induces its nuclear import. This novel intracellular signaling pathway suggests that changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart <ref> PMID:17923693 </ref>.

In cardiomyocytes, myopodin forms a Z-disc signaling complex with α-actinin, calcineurin, Ca<sup>2+</sup>/calmodulin-dependent kinase II (CaMKII), muscle-specific A-kinase anchoring protein, and myomegalin. Calcineurin keeps myopodin dephosphorylated preventing 14-3-3ß binding to myopodin. Upon activation of PKA/CaMKII or inhibition of calcineurin, myopodin undergoes phosphorylation, enabling its interaction with 14-3-3ß, which releases myopodin from the Z-disc-anchoring proteins and induces its nuclear import. This novel intracellular signaling pathway suggests that changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart <ref> PMID:17923693 </ref>.

[[Image:Myopodin interaction with Filamin C.jpg|700px]]

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==References==

[[Category: Z-disk]]

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 ==Introduction==
-The protein synaptopodin-2 (encoded by the gene SYNPO2[http://www.uniprot.org/uniprot/Q9UMS6]), also called "myopodin", genethonin-2, synaptopodin-like and fesselin, is together with synaptopodin and tritopodin/CHAP a member of the podin protein family.  It is widely expressed in striated, heart and smooth muscle cells where it localizes to Z-disks and dense bodies, respectively <ref name="r1"> PMID:11673475 </ref>. Myopodin is a multiadapter protein that interacts with filamentous actin, α-actinin and filamin. Different isoforms result from alternative splicing and alternative promoter usage and the predicted size of the resulting proteins varies between 74 kDa and 136 kDa; these variants show differential tissue distribution. The discrepancy between calculated molecular mass and apparent mobility in SDS-PAGE is at present still unclear, but might be due to post-translational modifications <ref> PMID:20554076 </ref> <ref> PMID:18371299 </ref> <ref> PMID:11696420</ref> <ref> PMID:12917631 </ref> <ref> PMID:18588515 </ref>. The lower molecular mass myopodin isoforms are dual compartment proteins that redistribute between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced manner <ref> PMID:C2150840 </ref>. Although its biological function is still undefined, recent findings support a role for myopodin as a z-disc multiadaptor protein (96).
+The protein synaptopodin-2 (encoded by the gene SYNPO2[http://www.uniprot.org/uniprot/Q9UMS6]), also called '''myopodin''', genethonin-2, synaptopodin-like and fesselin, is together with synaptopodin and tritopodin/CHAP a member of the podin protein family.  It is widely expressed in striated, heart and smooth muscle cells where it localizes to Z-disks and dense bodies, respectively <ref name="r1"> PMID:11673475 </ref>. Myopodin is a multiadapter protein that interacts with filamentous actin, α-actinin and filamin. Different isoforms result from alternative splicing and alternative promoter usage and the predicted size of the resulting proteins varies between 74 kDa and 136 kDa; these variants show differential tissue distribution. The discrepancy between calculated molecular mass and apparent mobility in SDS-PAGE is at present still unclear, but might be due to post-translational modifications <ref> PMID:20554076 </ref> <ref> PMID:18371299 </ref> <ref> PMID:11696420</ref> <ref> PMID:12917631 </ref> <ref> PMID:18588515 </ref>. The lower molecular mass myopodin isoforms are dual compartment proteins that redistribute between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced manner <ref> PMID:C2150840 </ref>. Although its biological function is still undefined, recent findings support a role for myopodin as a z-disc multiadaptor protein (96).
 ==Sequence Annotation==
-Myopodin contains one PPXY motif and multiple PXXP motifs <ref name="r1"> PMID:11673475 </ref>. Beside 2 lysine-rich NLS sites (consensus motif K-K/RX-K/R) myopodin provides 2 binding sites for 14-3-3(consensus motif a: RSXpS/TXP; b: RXXXpS/TXP Biophys Rev (2010) 2:181-189). These sites seem to be indispensable for effective shuttling of myopodin from the Z-disk into the nucleus <ref> PMCID:PMC2171942 </ref>. Phosphorylation of myopodin within the 14-3-3 binding sites (S225 and T272) by protein kinase A and Ca2+/calmodulin-dependent protein kinase II abrogates the binding with α -actinin and promotes the binding with 14-3-3 and importin α <ref> PMID:17923693 </ref>. Another important domain present in myopodin is the PDZ domain (postsynaptic density 95, discs large, and zonula occludens-1). PDZ domains are protein-protein interaction modules that can mediate multiple biological processes such as vesicle transport, ion channel signaling, and signal transduction in several tissues. PDZ domains in myopodin are of unknown function <ref> PMID:18371299 </ref>.
+Myopodin contains one PPXY motif and multiple PXXP motifs <ref name="r1"> PMID:11673475 </ref>. Beside 2 lysine-rich NLS sites (consensus motif K-K/RX-K/R) myopodin provides 2 binding sites for 14-3-3(consensus motif a: RSXpS/TXP; b: RXXXpS/TXP Biophys Rev (2010) 2:181-189). These sites seem to be indispensable for effective shuttling of myopodin from the Z-disk into the nucleus <ref> PMCID:PMC2171942 </ref>. Phosphorylation of myopodin within the 14-3-3 binding sites (S225 and T272) by protein kinase A and Ca<sup>2+</sup>/calmodulin-dependent protein kinase II abrogates the binding with α -actinin and promotes the binding with 14-3-3 and importin α <ref> PMID:17923693 </ref>. Another important domain present in myopodin is the PDZ domain (postsynaptic density 95, discs large, and zonula occludens-1). PDZ domains are protein-protein interaction modules that can mediate multiple biological processes such as vesicle transport, ion channel signaling, and signal transduction in several tissues. PDZ domains in myopodin are of unknown function <ref> PMID:18371299 </ref>.
@@ Line 22: / Line 22: @@
 A filamin-binding region was mapped to a fragment encompassing amino acids 240–521 of myopodin, i.e. a region that contains two of the previously described homology regions shared by myopodin and synaptopodin <ref> PMID:20554076 </ref>.
 Yeast two-hybrid analysis also identified an interaction  of myopodin with zyxin, which leads to slower migration of prostate cancer cells and reduced invasiveness <ref> PMID:16885336 </ref>.
-In cardiomyocytes, myopodin forms a Z-disc signaling complex with α-actinin, calcineurin, Ca2+/calmodulin-dependent kinase II (CaMKII), muscle-specific A-kinase anchoring protein, and myomegalin. Calcineurin keeps myopodin dephosphorylated preventing 14-3-3ß binding to myopodin. Upon activation of PKA/CaMKII or inhibition of calcineurin, myopodin undergoes phosphorylation, enabling its interaction with 14-3-3ß, which releases myopodin from the Z-disc-anchoring proteins and induces its nuclear import. This novel intracellular signaling pathway suggests that changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart <ref> PMID:17923693 </ref>.
+In cardiomyocytes, myopodin forms a Z-disc signaling complex with α-actinin, calcineurin, Ca<sup>2+</sup>/calmodulin-dependent kinase II (CaMKII), muscle-specific A-kinase anchoring protein, and myomegalin. Calcineurin keeps myopodin dephosphorylated preventing 14-3-3ß binding to myopodin. Upon activation of PKA/CaMKII or inhibition of calcineurin, myopodin undergoes phosphorylation, enabling its interaction with 14-3-3ß, which releases myopodin from the Z-disc-anchoring proteins and induces its nuclear import. This novel intracellular signaling pathway suggests that changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart <ref> PMID:17923693 </ref>.
 [[Image:Myopodin interaction with Filamin C.jpg|700px]]
@@ Line 32: / Line 32: @@
 ==References==
 <references/>
+[[Category: Z-disk]]