Protein and Lipid Composition of Radial Component‐Enriched CNS Myelin

Karthigasan, J.; Kosaras, Béla; Nguyen, Jack; Kirschner, Daniel A.

doi:10.1046/j.1471-4159.1994.62031203.x

Cited by 39 publications

(18 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phosphorylated form of MBP is enriched along with cytoskeletal proteins and kinases including MAPK, Fyn, and Lyn within insoluble Triton-X100 membrane domains when extracted from myelin [67,69,70]. These detergent-insoluble membrane domains from myelin also contain the radial component consisting of a series of tight junctions between myelin layers ( [71,72], see also [73]). …”

Section: Discussionmentioning

confidence: 99%

Classic 18.5- and 21.5-kDa Myelin Basic Protein Isoforms Associate with Cytoskeletal and SH3-Domain Proteins in the Immortalized N19-Oligodendroglial Cell Line Stimulated by Phorbol Ester and IGF-1

et al. 2012

View full text Add to dashboard Cite

The 18.5-kDa classic myelin basic protein (MBP) is an intrinsically disordered protein arising from the Golli (Genes of Oligodendrocyte Lineage) gene complex and is responsible for compaction of the myelin sheath in the central nervous system. This MBP splice isoform also has a plethora of post-translational modifications including phosphorylation, deimination, methylation, and deamidation, that reduce its overall net charge and alter its protein and lipid associations within oligodendrocytes (OLGs). It was originally thought that MBP was simply a structural component of myelin; however, additional investigations have demonstrated that MBP is multifunctional, having numerous protein-protein interactions with Ca 2+ -calmodulin, actin, tubulin, and proteins with SH3-domains, and it can tether these proteins to a lipid membrane in vitro. Here, we have examined cytoskeletal interactions of classic 18.5-kDa MBP, in vivo, using early developmental N19-OLGs transfected with fluorescently-tagged MBP, actin, tubulin, and zonula occludens 1 (ZO-1). We show that MBP redistributes to distinct 'membrane-ruffled' regions of the plasma membrane where it co-localizes with actin and tubulin, and with the SH3-domaincontaining proteins cortactin and ZO-1, when stimulated with PMA, a potent activator of the protein kinase C pathway. Moreover, using phospho-specific antibody staining, we show an increase in phosphorylated Thr98 MBP (human sequence numbering) in membrane-ruffled OLGs. CIHR Author ManuscriptCIHR Author Manuscript CIHR Author ManuscriptPreviously, Thr98 phosphorylation of MBP has been shown to affect its conformation, interactions with other proteins, and tethering of other proteins to the membrane in vitro. Here, MBP and actin were also co-localized in new focal adhesion contacts induced by IGF-1 stimulation in cells grown on laminin-2. This study supports a role for classic MBP isoforms in cytoskeletal and other protein-protein interactions during membrane and cytoskeletal remodeling in OLGs.

show abstract

Section: Discussionmentioning

confidence: 99%

Classic 18.5- and 21.5-kDa Myelin Basic Protein Isoforms Associate with Cytoskeletal and SH3-Domain Proteins in the Immortalized N19-Oligodendroglial Cell Line Stimulated by Phorbol Ester and IGF-1

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Actin and tubulin are present in compact myelin where they may be associated with MBP and the radial component, a series of tight junctions, containing claudin-11 [166], that pass through many layers of myelin [167]. MBP in solution causes polymerization of G-actin into filaments and bundling of the actin filaments [15,17,18,[109][110][111][112] (Fig.…”

Section: Mbp-mediated Interactions With Actin and Tubulin And Effect mentioning

confidence: 99%

“…Detergent extraction of myelin indicates that MBP is located in several different membrane domains or associated with different proteins. Some MBP distributes to two low-density glycosphingolipid/cholesterol-enriched Triton X-100-insoluble fractions, one of which is associated with actin, tubulin, caveolin, and kinases [167,[194][195][196]. Some MBP is also found in the Triton X-100 supernatant associated with MAG, PLP, MAPK, and some phospholipid [197].…”

Section: Mbp-cytoskeleton Interactions In Vivomentioning

confidence: 99%

Myelin basic protein: a multifunctional protein

Boggs

2006

Cell. Mol. Life Sci.

558

View full text Add to dashboard Cite

Myelin basic protein (MBP), the second most abundant protein in central nervous system myelin, is responsible for adhesion of the cytosolic surfaces of multilayered compact myelin. A member of the 'intrinsically disordered' or conformationally adaptable protein family, it also appears to have several other functions. It can interact with a number of polyanionic proteins including actin, tubulin, Ca(2+)-calmodulin, and clathrin, and negatively charged lipids, and acquires structure on binding to them. It may act as a membrane actin-binding protein, which might allow it to participate in transmission of extracellular signals to the cytoskeleton in oligodendrocytes and tight junctions in myelin. Some size isoforms of MBP are transported into the nucleus and thus they may also bind polynucleotides. Extracellular signals received by myelin or cultured oligodendrocytes cause changes in phosphorylation of MBP, suggesting that MBP is also involved in signaling. Further study of this very abundant protein will reveal how it is utilized by the oligodendrocyte and myelin for different purposes.

show abstract

“…Their expression is enriched during active early myelination in the human and mouse, and in immature OLGs in culture [5][6][7]. These minor MBP isoforms have been observed in the nucleus of primary OLG cultures and OLGs in the mouse brain [25][26][27] and are also enriched in the radial component of compact myelin [28,29]. We have found that full-length 21.5-kDa MBP was still localized primarily to the nucleus despite the presence of the 3′UTR [20][21][22].…”

Section: Introductionmentioning

confidence: 70%

The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear-localization signal

Smith

Seymour

Boggs

et al. 2012

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The predominant 18.5-kDa classic myelin basic protein (MBP) is mainly responsible for compaction of the myelin sheath in the central nervous system, but is multifunctional, having numerous interactions with Ca 2+ -calmodulin, actin, tubulin, and SH3-domains, and can tether these proteins to a lipid membrane in vitro. The full-length 21.5-kDa MBP isoform has an additional 26 residues encoded by exon-II of the classic gene, which causes it to be trafficked to the nucleus of oligodendrocytes (OLGs). We have performed site-directed mutagenesis of selected residues within this segment in red fluorescent protein (RFP)-tagged constructs, which were then transfected into the immortalized N19-OLG cell line to view protein localization using epifluorescence microscopy. We found that 21.5-kDa MBP contains two nontraditional PYnuclear-localization signals, and that arginine and lysine residues within these motifs were involved in subcellular trafficking of this protein to the nucleus, where it may have functional roles during myelinogenesis.

show abstract

Protein and Lipid Composition of Radial Component‐Enriched CNS Myelin

Cited by 39 publications

References 37 publications

Classic 18.5- and 21.5-kDa Myelin Basic Protein Isoforms Associate with Cytoskeletal and SH3-Domain Proteins in the Immortalized N19-Oligodendroglial Cell Line Stimulated by Phorbol Ester and IGF-1

Classic 18.5- and 21.5-kDa Myelin Basic Protein Isoforms Associate with Cytoskeletal and SH3-Domain Proteins in the Immortalized N19-Oligodendroglial Cell Line Stimulated by Phorbol Ester and IGF-1

Myelin basic protein: a multifunctional protein

The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear-localization signal

Contact Info

Product

Resources

About