Myelination and Demyelination pp 85-96 | Cite as
Molecular Genetics of Myelin Proteolipid Proteins and Their Expression in Normal and Jimpy Mice
Abstract
Myelin proteolipid protein (PLP) is one of the most abundant proteins in myelin of the central nervous system (CNS), and together with myelin basic protein (MBP), constitutes 80% of the myelin membrane proteins of the CNS. It is called “proteolipid” because of its unusual property to dissolve in organic solvents (5). There is another less abundant proteolipid, DM20, which shows immunological cross-reactivity with the major proteolipid protein (13). Most investigators have obtained molecular weights of 24,000–26,000 for PLP by SDS-PAGE, and approximately 5,000 less than PLP for DM20 (13). Lipids are covalently attached to PLP via an 0-ester linkage (28). Because amino acid and nucleotide sequences of PLP are remarkably well conserved among mouse, rat, cow, and human (4, 6, 8, 9, 14, 16, 20, 21, 25) and because severe dysmyelination is observed in the animals whose PLP-synthesis are affected (7), PLP is thought to play a crucial role in myelination in the CNS; probably by promoting the apposition of extracellular surfaces of the myelin lamellae.
Keywords
Myelin Basic Protein Transcription Initiation Site Polyadenylation Site Proteolipid Protein Primer Extension AnalysisPreview
Unable to display preview. Download preview PDF.
References
- 1.Beraducci A, Peterson AC, Aguayo AJ: Oligodendrocyte mosaicism in the CNS of jimpy normal mouse chimaerass. Neurology 31:118, 1981Google Scholar
- 2.Chou J, Roizman B: Isomerization of Herpes Simplex Virus 1 genome: Identification of the cis-acting and recombination sites within the domain of the a sequence. Cell 41:803, 1985PubMedCrossRefGoogle Scholar
- 3.Dautigny A, Maattei M-G, Morello D, Alliel PM, Pham-Dinh D, Amar L, Arnoud D, Simon D, Mattel J-F, Guenet J-L, Jolles P, Avner P: The structural gene coding for myelin-associated proteolipid protein is mutated in jimpy mice. Nature 321:867, 1986PubMedCrossRefGoogle Scholar
- 4.Diehl H-J, Schaich M, Budzinski R-M, Stoffel W: Individual exons encode the integral membrane domains of human myelin proteolipid protein. Proc Natl Acad Sci 83:9807, 1986PubMedCrossRefGoogle Scholar
- 5.Folch J, Lees M: Proteolipids: a new type of tissue lipoproteins. J Biol Chem 191:807, 1951PubMedGoogle Scholar
- 6.Gardinier MV, Macklin WB, Diniak AJ, Deininger PL: Characterization of myelin proteolipid mRNAs in normal and jimpy mice. Mol Cell Biol 6:3755, 1986PubMedGoogle Scholar
- Hogan EL, Greenfield S: Animal models of genetic disorders of myelin. In Myelin (Morell P, ed.) Plenum Press, New York, pp 489–534, 1984Google Scholar
- 8.Hudson LD, Berndt JA, Puckett C, Kozak CA, Lazzarini RA: Aberrant splicing of proteolipid protein mRNA in the dysmyelinating jimpy mutant mouse. Proc Natl Acad Sci 84:1454, 1987PubMedCrossRefGoogle Scholar
- 9.Ikenaka K, Furuichi T, Iwasaki Y, Moriguchi A, Okano H, Mikoshiba K: Myelin proteolipid protein gene structure and its regulation of expression in normal and jimpy mutant mice. J Mol Biol 199:587, 1988CrossRefGoogle Scholar
- 10.Knapp PE, Skoff RP, Redstone DW: Oligodendroglial cell death in jimpy mice: An explanation for the myelin deficit. J Neurosci 6:2813, 1986PubMedGoogle Scholar
- 11.Knapp PE, Bartlett WP, Skoff RP: Cultured oligodendrocytes mimic in vivo phenotypic characteristics: Cell shape, expression of myelin-specific antigens, and membrane production. Develop Biol 120:356, 1987PubMedCrossRefGoogle Scholar
- 12.Kristensson K, Zeller NK, Dubois-Dalcq ME, Lazzarini RA: Expression of myelin basic protein gene in the developing rat brain as revealed by in situ hybridization. J Histochem Cytochem 34:467, 1986PubMedCrossRefGoogle Scholar
- 13.Lees MB, Brostoff SW: Proteins of myelin. In Myelin (Morell P, ed.) Plenum Press, New York, pp 197–217, 1984Google Scholar
- 14.Macklin WB, Campagnoni CW, Deininger PL, Gardinier MV: Structure and expression of the mouse myelin proteolipid protein gene. J Neurosci Res 18:383, 1987PubMedCrossRefGoogle Scholar
- 15.Macklin WB, Gardinier MV, King KD, Kampf K: An AG-GG transition at a splice site in the myelin proteolipid protein gene in j impy mice results in the removal of an exon. FEBS Letters 223:417, 1987PubMedCrossRefGoogle Scholar
- 16.Milner RJ, Lai C, Nave K-A, Lenoir D, Ogata J, Sutcliffe JG: Nucleotide sequences of two mRNAs for rat brain myelin proteolipid protein. Cell 42:931, 1985PubMedCrossRefGoogle Scholar
- 17.Morello D, Pham-Dinh D, Jolles P: Myelin proteolipid protein (PLP and DM-20) transcripts are deleted in jimpy mutant mice. EMBO J 5:3489, 1986PubMedGoogle Scholar
- 18.Moriguchi A, Ikenaka K, Furuichi T, Okano H, Iwasaki Y, Mikoshiba K: The fifth exon of the myelin proteolipid protein-coding gene is not utilized in the brain of j impy mutant mice. Gene 55:333, 1987PubMedCrossRefGoogle Scholar
- 19.Nagaike K, Mikoshiba K, Tsukada Y: Dysmye 1 ination of Shiverer mutant mice in vivo and in vitro. J Neurochem 39:1235, 1982PubMedCrossRefGoogle Scholar
- 20.Naismith AL, Hoffman-Chudzik E, Tsui L-C, Riordan JR: Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA. Nucleic Acids Res 13:7413, 1985PubMedCrossRefGoogle Scholar
- 21.Nave K-A, Lai C, Bloom FE, Milner RJ: Jimpy mutant mouse: A 74-base deletion in the mRNA for myelin proteolipid protein and evidence for a primary defect in RNA splicing. Proc Natl Acad Sci 83:9264, 1986PubMedCrossRefGoogle Scholar
- 22.Nave K-L, Lai C, Bloom FE, Milner RJ: Splice site selection in the proteolipid protein (PLP) gene transcript and primary structure of the DM-20 protein of central nervous system myelin. Proc Natl Acad Sci 84:5665, 1987PubMedCrossRefGoogle Scholar
- 23.Nave K-L, Bloom FE, Milner RJ: A single nucleotide difference in the gene for myelin proteolipid protein defines the jimpy mutation in mouse. J Neurochem 49:1873, 1987PubMedCrossRefGoogle Scholar
- 24.Okano H, Miura M, Moriguchi A, Ikenaka K, Tsukada Y, Mikoshiba K: Inefficient transcription of the myelin basic protein gene possibly causes hypomye 1 ination in myelin deficient mutant mice. J Neurochem 48:470, 1987PubMedCrossRefGoogle Scholar
- 25.Puckett C, Hudson L, Ono K, Friedrich V, Benecke J, Dubois-Dalcq M, Lazzarini RA: Myelin-specific proteolipid protein is expressed in myelinating Schwann cells but is not incorporated into myelin sheaths. J Neurosci Res 18:511, 1987PubMedCrossRefGoogle Scholar
- 26.Schwöb VS, Clark HB, Agrawal D, Agrawal HC: Electron microscopic immunocytochemical localization of myelin proteolipid protein and myelin basic protein to oligodendrocytes in rat brain during myelination. J Neurochem 45:559, 1985PubMedCrossRefGoogle Scholar
- 27.Sorg BA, Smith MM, Campagnoni AT: Developmental expression of the myelin proteolipid protein and basic protein mRNAs in normal and dysmye1inating mutant mice. J Neurochem 49:1146, 1987PubMedCrossRefGoogle Scholar
- 28.Stoffyn P, Folch J: On the type of linkage binding fatty acids present in brain white matter proteolipid apoprotein. Biochem Biophys Res Commun 44:157, 1971PubMedCrossRefGoogle Scholar
- 29.Trapp BD, Moench T, Pulley M, Barbosa E, Tennekoon, Griffin J: Spatial segregation of mRNA encoding myelin-specific proteins. Proc Natl Acad Sci 84:7773, 1987PubMedCrossRefGoogle Scholar
- 30.Varmuza SL, Smiley JR: Signals for site-specific cleavage of HSV DNA: Maturation involves two separate cleavage events at sites distal to the recognition sequences. Cell 41:793, 802, 1985Google Scholar
- 31.Willard HF, Riordan JR: Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders. Science 230:940, 1985PubMedCrossRefGoogle Scholar