Abstract
Historically synemin has been studied as an intermediate filament protein. However, synemin also binds the type II regulatory (R) subunit α of protein kinase A (PKA) and protein phosphatase type 2A, thus participating in the PKA and phosphoinositide 3-kinase (PI3K)-Akt and signaling pathways. In addition, recent studies using transgenic mice indicate that a significant function of synemin is its role in signaling pathways in various tissues, including the heart. Recent clinical reports have shown that synemin mutations led to multiple cases of dilated cardiomyopathy. Additionally, a single case of the rare condition ulnar-mammary-like syndrome with left ventricular tachycardia due to a mutation in the synemin gene (SYNM) has been reported. Therefore, this review uses these recent studies to provide a new framework for detailed discussions on synemin tissue distribution, binding partners and synemin in disease. Differences between α- and β-synemin are highlighted. The studies presented here indicate that while synemin does function as an intermediate filament protein, it is unique among this large family of proteins as it is also a regulator of signaling pathways and a crosslinker. Also evident is that the dominant function(s) are isoform-, developmental-, and tissue-specific.
Highlights
Synemin is an unusual and exotic intermediate filament (IF) protein that has functions which extend past the normal role of IF proteins
Synemin was first identified as an IF-associated protein (IFAP)
This role for synemin as an a-kinase anchoring protein (AKAP) would explain why a loss of synemin in null mice resulted in increased protein kinase A (PKA) activity which resulted in an increase in phosphorylation of PKA substrates (RIIα, cAMP Responsive Element Binding Protein 1 (CREB1), and ribosomal protein S6)
Summary
Synemin is an unusual and exotic intermediate filament (IF) protein that has functions which extend past the normal role of IF proteins. Synemin is considered “exotic” since it is the only cytoplasmic IF representative currently identified that undergoes alternative splicing (Herrmann and Aebi, 2004; Welch et al, 2010). Another unusual characteristic of synemin is its wide tissue distribution. In atypical fashion for an IF protein, synemin is found in other (non-junctional) membrane locations in astrocytoma cells and cardiac myocytes
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