Human synemin gene generates splice variants encoding two distinct intermediate filament proteins

Abstract

Intermediate filament (IF) proteins are constituents of the cytoskeleton, conferring resistance to mechanical stress, and are encoded by a dispersed multigene family. In man we have identified two isoforms (180 and 150 kDa) of the IF protein synemin. Synemin a and b have a very short N-terminal domain of 10 amino acids and a long C-terminal domain consisting of 1243 amino acids for the a isoform and 931 amino acids for the b isoform. An intronic sequence of the synemin b isoform is used as a coding sequence for synemin a. Both mRNA isoforms (6.5 and 7.5 kb) result from alternative splicing of the same gene, which has been assigned to human chromosome 15q26.3. Analyses by Northern and Western blot revealed that isoform b is the predominant isoform in striated muscles, whereas both isoforms (a and b) are present in almost equal quantities in smooth muscles. Co-transfection and immunolabeling experiments indicate that both synemin isoforms are incorporated with desmin to form heteropolymeric IFs. Furthermore synemin and desmin are found aggregated together in certain pathological situations.

Plectin 1 links intermediate filaments to costameric sarcolemma through β-synemin, α-dystrobrevin and actin

“…Comparison of the previously reported human and the present rat sequences revealed an overall identity of 72.4%. Desmuslin has subsequently been referred to as β-synemin (Mizuno et al, 2004;Titeux et al, 2001), and this name is also used in this article. The interactions of plectin with β-synemin and then α-dystrobrevin, a dystrophin-associated protein, agreed with our previous findings of the association of plectin threads with dystrophin-containing dense plaques.…”

“…β-Synemin is a constituent of heteropolymeric IF in muscles, and has a very short N-terminal head domain, a central α-helical rod domain conserved in all IF proteins, and a very long C-terminal tail domain (Titeux et al, 2001). β-synemin molecules are assumed to link IFs to DGC, based on the in vitro findings that they can bind α-dystrobrevin, dystrophin and desmin (Bhosle et al, 2006;Mizuno et al, 2001).…”

Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

“…Desmuslin is an IF protein recently characterized from the dystrophin complex that associates with α-dystrobrevin in costameres and with desmin in costameres and around the Z-line (39). But sequence homology suggests that desmuslin may be the human homologue of synemin, more specifically of the smaller synemin ß transcript (40). Syncoilin is another dystrophinassociated protein that seems to concentrate in neuromuscular junctions (41).…”

Intermediate filament dynamics and breast cancer: Aberrant promoter methylation of the Synemin gene is associated with early tumor relapse

“…The protein is widely expressed in most mammalian contractile cell types derived from the mesoderm and ectoderm, such as the heart, skeletal and small intestine muscle (Granger and Lazarides, 1980;Bilak et al, 1998;Mizuno et al, 2001;Titeux et al, 2001;Hirako et al, 2003) and also in certain noncontractile cells, such as glial cells and lens (Tawk et al, 2003). Recently, it has become clear that SYNM contains binding motifs for various microfilamentassociated polypeptides such as a-actinin and vinculin, enabling the connection of IFs to microfilaments in the cytoskeleton context (Bellin et al, 1999(Bellin et al, , 2001Mizuno et al, 2001).…”