Synemin Isoforms in Astroglial and Neuronal Cells from Human Central Nervous System

Abstract

The intermediate filament (IF) synemin gene encodes three IF proteins (H 180, M 150, L 41 kDa) with overlapping distributions. Synemin M was present early with vimentin and nestin. Synemin H was found later in the nervous system and mesodermic derivatives concomitantly with angiogenesis and the migration of neural crest cells. Synemin L appeared later in neurons. A series of in vitro cell cultures were done to identify the linkage between synemin isoforms and specific cell types of the central nervous system (CNS). The neurons and glia from the brains of humans and rats were cultured and double immunostaining done with antibodies against the H/M or L synemin isoforms and neural cell types (betaIII-tubulin or NeuN) or astrocyte intermediate filaments (GFAP or vimentin). In neurons of the CNS, synemin H/M were co-expressed with GFAP, vimentin or nestin in glial cells, whereas synemin L was found in neurons.

Roles and Potential Clinical Applications of Intermediate Filament Proteins in Brain Tumors

“…6,7 In addition, during the maturation of radial glial cells into astrocytes, synemin is transiently expressed. 8,9 Although most mature astrocytes express GFAP only, subpopulation of astrocytes, such as Bergman glial cells, may coexpress GFAP together with vimentin. 6 Of note, mature oligodendrocytes do not appear to contain cytoplasmic IF proteins, 6 perhaps because of the scarcity of their cytoplasm.…”

“…They are mostly present in stem and progenitor cells, although synemin and nestin are also found in differentiated muscle cells and endothelial cells, respectively. 1,5,8,9 Although IFs enable tissues to withstand mechanical challenges, at the cellular level, IF proteins regulate signaling pathways and modulate cellular behaviors such as apoptosis and resistance to metabolic stress. 1,4,5 Mutations in genes coding for IF proteins are responsible for approximately 100 rare human genetic diseases, including epidermolysis and keratoderma disorders, cardiopathies and myopathies, lipodystrophies, neurologic disorders such as Alexander disease and Charcot-Marie-Tooth disease, and accelerated aging.…”

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

“…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).…”

Peripherin partially localizes in Bunina bodies in amyotrophic lateral sclerosis

“…Supposing that normally spliced peripherin had originally been present in Bunina bodies, the antibody used in this study would not have always recognized peripherin. Alternatively spliced isoforms are also described for other IF proteins including GFAR and synemin [8]. The third theory is as follows; typical Bunina bodies consist of amorphous electrondense material surrounded by tubular and vesicular structures, occasionally demonstrating a few clear central areas on electron microscopic analysis [28].…”

“…Peripherin can co-assemble with neurofilaments (NFs) [3], and expresses predominantly in neurons of the peripheral nervous system and also in those of the central nervous system including spinal motor neurons [4]. Mutations of the gene encoding IF proteins such as keratin [5], GFAP [6], desmin [7] and the low-molecular weight subunit of NF [8] have been linked to skin disorders, Alexander's disease, myopathy and Charcot-Marie-Tooth type 2E, respectively. Many IF protein diseases are characterized by the presence of intracytoplasmic IF protein inclusions.…”