Expression of Sarcoglycans in the Human Cerebral Cortex: An Immunohistochemical and Molecular Study

Abstract

The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, β, δ, γ, εand ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of εand ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.

An Immunofluorescence Study About Staining Pattern Variability of Sarcoglycans in Rat’s Cerebral and Cerebellar Cortex

“…The present report has shown that in rat's cerebral and cerebellar cortex, besides ε-and ζ-sarcoglycans, the α-, β-, γand δ-sarcoglycans are present too. These results showing the presence of sarcoglycans in rat's brain, are in accordance with an our previous report which has demonstrated the presence of all sarcoglycans in human intrasurgical biopsies of cerebral cortex, both in neuronal and glial cells [21]. Different report show that ε-sarcoglycan is present around pyramidal cells of different brain regions and in particular it is around the soma of dopaminergic (DAergic) and serotonergic (5-HTergic) cell groups; in the cerebellum, ε-sarcoglycan has been found around in the Purkinje cell layer and molecular layer, but it has been found absent in the granular layer [18].…”

“…Furthermore, it was hypothesized the existence of a "DGC-like" characteristic of the brain, involved in postsynaptic clustering and stabilization of some inhibitory GABAergic synapses, which is made up of the entire dystroglycan sub-complex and the entire sarcoplasmic sub-complex whereas the sarcoglycan sub-complex is formed only by ε-and ζ-sarcoglycan nevertheless, for this author, although theoretically possible, the existence of a prototypical tetrameric sarcoglycan complex in brain is unlikely [20]. Instead, an our recent report, has demonstrated the expression of α-, β-, γ-, δ-and ε-sarcoglycans in human cerebral cortex [21] demonstrating a difference between molecular results and immunofluorescence results when the biopsies have not been extracted from same region of the brain [21]. On this basis, in the present report, by immunofluorescence, we verify the presence of sarcoglycans in rat's cerebral and cerebellar cortex; moreover, we verify if these proteins show an uniformly expression or if a different distribution pattern among the cerebral cortex areas and in cerebellar cortex exists.…”

The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels

“…It interacts with the DG and is part of the Dystrophin-associated protein complex (DAPC), bridging the extracellular matrix to the actin cytoskeleton and ensuring membrane stability and force transduction during muscle contraction (Constantin, 2014 ). In the brain, SG units have been found in the membranes and the cytoplasm of some large cortical neurons as well as in some astrocyte cell bodies (Anastasi et al, 2012 ). However, the presence of a SGC in the cerebrovascular system had never been documented.…”

The genetics of dystonia: new twists in an old tale

“…With the recent identification of TUBB4A as the cause of whispering dysphonia, the function of several genes now point to cell structure as playing an important role in dystonia. TUBB4A encodes tubulin, the major component of the cytoskeleton; torsin A appears to be important for the structure of the nuclear envelope where it may form a bridge complex between it and the cytoskeleton (Atai et al , 2012) and also interacts with vimentin, a type III intermediate filament important for motility, chemotaxis, adhesion, intracellular signalling and neurite outgrowth (Hewett et al , 2006); and SGCE , a gene linked to myoclonus-dystonia, encodes a member of the dystrophin-glycoprotein complex that connects the cytoskeleton to the extracellular matrix in muscle and may play a role in synaptic organization in the CNS (Anastasi et al , 2012). Synaptic dysfunction is also highlighted by the recent identification of PRRT2 , the protein product of which interacts with the SNARE protein, SNAP25 (Lee et al , 2012), in addition to evidence suggesting torsin A may regulate vesicular traffic and, by extension, neurotransmitter turnover (Warner et al , 2010).…”