Different expression of synemin isoforms in glia and neurons during nervous system development

Abstract

The synemin gene encodes proteins belonging to the intermediate filament family. These proteins confer resistance to mechanical stress and modulate cell shape. Three synemin isoforms, of 180 (H), 150 (M) and 41 (L) kDa, are produced by alternative splicing of the pre-mRNA and are regulated differently during development. The three isoforms differ in their C-terminal tail domains, while their IF rod domains are identical. Synemins H/M occurred together with nestin and vimentin in glial progenitors during the early differentiation of the developing mouse central nervous system. They are later found in GFAP-labeled cells. In contrast, the L isoform appeared only in neurons, together with neurofilaments and betaIII-tubulin in the brain after birth. However, synemin L appeared from E13 in the peripheral nervous system, where it was confined to the neurons of spinal ganglia. In the meantime, the synemin H/M isoforms were found in both the neurons and Schwann cells of the sensorial ganglia from E11. Tissue fractionation and purification of IFs from adult mouse spinal cord revealed that the synemin L isoform binds to neurofilaments associated with the membrane compartment. This report describes the synthesis of the three synemin isoforms by selective cell types, and their temporal and spatial distributions. Mechanisms specific to neurons and glia probably control the splicing of the common synemin mRNA and the synthesis of each synemin isoform.

Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks

“…1A-B) and 14 days (data not shown) after lesioning. No synemin immunoreactivity was seen on the uninjured site (data not shown), which is in agreement with recent findings showing that ␣-and ␤-synemin are not present in the dentate gyrus of normal, adult mice (Izmiryan et al, 2006). Synemin and GFAP immunoreactivity colocalized in reactive astrocytes both in the denervated dentate gyrus (Fig.…”

Synemin acts as a regulator of signalling molecules in skeletal muscle hypertrophy

“…Interestingly, this membrane defect could be indirectly related to the absence of synemin and be the result of perturbation of its interaction with proteins that might be directly involved in the integrity of membrane structure, such as dystrophin, utrophin, adystrobrevin, plectin 1, zyxin, vinculin and talin (Bellin et al, 1999;Bhosle et al, 2006;Hijikata et al, 2008;Mizuno et al, 2001;Sun et al, 2008a;Sun et al, 2008b;Sun et al, 2010a). It has been reported that b-synemin mediates the association of desmin IFs with Z-lines in neonate cardiomyocytes, whereas a-synemin stabilises junctional complexes between cardiomyocytes (Lund et al, 2012), and synemin L binds to neurofilaments associated with the membrane compartment in adult mouse spinal cord (Izmiryan et al, 2006). We cannot know yet which synemin isoform is more important for membrane integrity because our Synm 2/2 model is null for all forms of synemin.…”

“…An exception is the protein synemin. First identified as a high-molecular-mass protein associated with desmin and vimentin filaments in muscle (Granger and Lazarides, 1980), synemin expression was later detected in different tissues and cell types, including the nervous system, endothelial cells, retinal cells and hepatic stellate cells (Hirako et al, 2003;Izmiryan et al, 2006;Izmiryan et al, 2009;Izmiryan et al, 2010;Schmitt-Graeff et al, 2006;Tawk et al, 2003;Uyama et al, 2006). Three synemin isoforms differing in their C-terminal tails -a-synemin (also known as synemin H, 180 kDa), b-synemin (also known as synemin M, 150 kDa) and synemin L (41 kDa) -are produced by alternative splicing and are differentially regulated during embryonic development (Titeux et al, 2001;Xue et al, 2004).…”

“…Consequently, synemin filaments are unstable and delocalised in the cells of mice lacking desmin or vimentin (Carlsson et al, 2000;Izmiryan et al, 2006;Izmiryan et al, 2009;Jing et al, 2007;Xue et al, 2004). Synemin also interacts with a-actinin, plectin 1, zyxin, and three components of the dystrophin-associated protein complex, dystrophin, utrophin and a-dystrobrevin (Bellin et al, 1999;Bhosle et al, 2006;Hijikata et al, 2008;Mizuno et al, 2001;Sun et al, 2010a).…”

The polypeptide composition of moving and stationary neurofilaments in cultured sympathetic neurons

“…One possibility is that there is an additional neurofilament subunit, as yet unidentified, that interacts with the neurofilament motors and that this subunit is common to all neurofilaments. In fact, recent studies indicate that neurons may also express an alternately spliced isoform of the intermediate filament protein synemin, termed synemin L [Izmiryan et al, 2006], so it is quite possible that we do not yet know the full extent of the complexity of neurofilament composition. However, it seems more likely that the neurofilament motors are capable of interacting with multiple different neurofilament protein subunits.…”