Identification and characterization of a B-cell determinant within the amphipathic domain (residues 178-238) of the myelin proteolipid protein

Stephens, Tyler; Pákáski, Magdolna; Lees, Marjorie B.; Potter, Nicholas

doi:10.1002/(sici)1097-4547(19960301)43:5<545::aid-jnr4>3.0.co;2-i

Cited by 6 publications

(1 citation statement)

References 50 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the myelin membrane, exposure of this segment at the extracellular interface may place it in a favorable position to interact with partner proteolipid molecules emanating from the opposite bilayer. In support of this notion, Stephens et al (1996) have recently found that the c-d loop of PLP and, in particular, of amino acids 209 -217, is a common B-cell determinant for many antimyelin and anti-PLP sera, which recognize the epitope on live and fixed mouse oligodendrocytes in culture and paraformaldehyde-fixed brain sections.…”

Section: Point Mutations In the C-d Loop Of Dm-20/plp Eradicate Bindimentioning

confidence: 91%

Conservation of Topology, But Not Conformation, of the Proteolipid Proteins of the Myelin Sheath

et al. 1997

View full text Add to dashboard Cite

The proteolipid protein gene products DM-20 and PLP are adhesive intrinsic membrane proteins that make up >/=50% of the protein in myelin and serve to stabilize compact myelin sheaths at the extracellular surfaces of apposed membrane lamellae. To identify which domains of DM-20 and PLP are positioned topologically in the extracellular space to participate in adhesion, we engineered N-glycosylation consensus sites into the hydrophilic segments and determined the extent of glycosylation. In addition, we assessed the presence of two translocation stop-transfer signals and, finally, mapped the extracellular and cytoplasmic dispositions of four antibody epitopes. We find that the topologies of DM-20 and PLP are identical, with both proteins possessing four transmembrane domains and N and C termini exposed to the cytoplasm. Consistent with this notion, DM-20 and PLP contain within their N- and C-terminal halves independent stop-transfer signals for insertion into the bilayer of the rough endoplasmic reticulum during de novo synthesis. Surprisingly, the conformation (as opposed to topology) of DM-20 and PLP may differ, which has been inferred from the divergent effects that many missense mutations have on the intracellular trafficking of these two isoforms. The 35 amino acid cytoplasmic peptide in PLP, which distinguishes this protein from DM-20, imparts a sensitivity to mutations in extracellular domains. This peptide may normally function during myelinogenesis to detect conformational changes originating across the bilayer from extracellular PLP interactions in trans and trigger intracellular events such as membrane compaction in the cytoplasmic compartment.

show abstract

Section: Point Mutations In the C-d Loop Of Dm-20/plp Eradicate Bindimentioning

confidence: 91%

Conservation of Topology, But Not Conformation, of the Proteolipid Proteins of the Myelin Sheath

et al. 1997

View full text Add to dashboard Cite

show abstract

Orientation of myelin proteolipid protein in the oligodendrocyte cell membrane

et al. 1996

View full text Add to dashboard Cite

The orientation of proteins within a cell membrane can often be difficult to determine. A number of models have been proposed for the orientation of the myelin protein, proteolipid protein (PLP), each of which includes exposed domains on the intracellular and extracellular membrane faces. Immunolabeling experiments have localized the C-terminus and the region spanning amino acids 103-116 to the cytoplasmic face of the membrane, but no well characterized antibodies have been available that label extracellular PLP domains. In this report, we describe the generation and characterization of mouse monoclonal antibodies (mAb) against putative extramembrane domains. Three of the mAb, specific for PLP peptides 40-59, 178-191, or 215-232, immunostain live oligodendrocytes, indicating that these regions of the molecule are exposed on the external surface of the cell. In addition, we have used these mAb to study the time-course of incorporation of PLP into the oligodendrocyte membrane. These studies increase our knowledge of the orientation of PLP in the lipid bilayer and are relevant for understanding myelin function.

show abstract

Four different synthetic peptides of proteolipid protein induce a distinct antibody response in MP4-induced experimental autoimmune encephalomyelitis

Recks

Grether

Broeck

et al. 2015

Clinical Immunology

View full text Add to dashboard Cite

Identification and characterization of a B-cell determinant within the amphipathic domain (residues 178-238) of the myelin proteolipid protein

Cited by 6 publications

References 50 publications

Conservation of Topology, But Not Conformation, of the Proteolipid Proteins of the Myelin Sheath

Conservation of Topology, But Not Conformation, of the Proteolipid Proteins of the Myelin Sheath

Orientation of myelin proteolipid protein in the oligodendrocyte cell membrane

Four different synthetic peptides of proteolipid protein induce a distinct antibody response in MP4-induced experimental autoimmune encephalomyelitis

Contact Info

Product

Resources

About