Molecular cloning and nucleotide sequence of a cDNA clone coding for rat brain myelin proteolipid

Dautigny, André; Alliel, Patrick M.; d'Auriol, L; Dinh, D. Pham; Nussbaum, J.L.; Galibert, Francis; Joliés, P.

doi:10.1016/0014-5793(85)80869-3

Cited by 60 publications

(30 citation statements)

References 17 publications

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“…1). Our predicted sequence is in very good agreement with the previously determined portions of rat PLP sequence and with other rat cDNA clones (11,27). It is of interest that, as in the rat, multiple PLP-specific mRNAs are found in the mouse.…”

Section: Discussionsupporting

confidence: 87%

“…The expression of these myelin proteins correlates closely with the formation of myelin in the developing rat brain, and mouse mutants that are defective in myelin formation show lowered levels of these myelin proteins (4,14,20,25 expression and the genetic deficiency in the shiverer mouse myelination mutant (12,34,44). Several groups have recently isolated cDNA clones for the other major myelin protein, PLP, and have studied PLP mRNAs in bovine and rat tissue (11,13,27, 29). The current studies were undertaken to isolate PLP cDNA clones for studies on the developmental regulation of PLP expression in mice.…”

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confidence: 99%

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Characterization of myelin proteolipid mRNAs in normal and jimpy mice.

Gardinier¹,

Macklin²,

Diniak³

et al. 1986

Mol. Cell. Biol.

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A clone specific for the rat myelin proteolipid protein (PLP) was isolated from a cDNA library made in pUC18 from 17-day-old rat brain stem mRNA. This clone corresponded to the carboxyl-terminal third of the PLP-coding region. The clone was used to identify PLP-specific mRNAs in mouse brain and to establish the time course of PLP mRNA expression during mouse brain development. Three PLP-specific mRNAs were seen, approximately 1,500, 2,400, and 3,200 bases in length, of which the largest was the most abundant. During brain development, the maximal period of PLP mRNA expression was from 14 to 25 days of age, and this was a similar time course to that for myelin basic protein mRNA expression. When the jimpy mouse, an X-linked dysmyelination mutant, was studied for PLP mRNA expression, low levels of PLP mRNA were seen which were approximately 5% of wild-type levels at 20 days of age. When jimpy brain RNA was analyzed by Northern blotting, the PLP-specific mRNA was shown to be 100 to 200 bases shorter than the wild-type PLP-specific mRNA. This size difference was seen in the two major PLP mRNAs, and it did not result from a loss of polyadenylation of these mRNAs.The biosynthesis of the myelin sheath is a crucial part of nervous system development, and as a result, the developmental expression of the myelin protein genes is highly regulated. The normal pattern of myelin protein expression in rodents indicates that little myelin protein expression occurs prenatally or in neonatal animals (2,5,6,8,23,26,28) and that myelin protein synthesis and accumulation increase significantly in the brain at about 10 days after birth, reaching a peak between 15 and 22 days after birth (2,5,6,8,23).Central nervous system myelin contains two major classes of proteins, myelin basic protein (MBP) and proteolipid protein (PLP), which together constitute as much as 80% of the total myelin protein (15,30). The four MBPs that are present in rodent myelin have homologous amino acid sequences, including identical amino-and carboxyl-terminal sequences but internal segments of unique amino acid sequence (3). They are translated from four different mRNAs (50), and the four MBP mRNAs can be produced from a single MBP gene by alternative mRNA splicing (12,44). Two PLPs are present in myelin, the major PLP, which has an apparent molecular weight of 25,000, and the closely related proteolipid DM20 (1), which has an apparent molecular weight of 20,000. PLP and DM20 may have a relationship similar to that found among the four MBPs, since they have identical amino-and carboxyl-terminal sequences (46), and they are very closely related by amino acid composition and by antigenic characteristics. The expression of these myelin proteins correlates closely with the formation of myelin in the developing rat brain, and mouse mutants that are defective in myelin formation show lowered levels of these myelin proteins (4,14,20,25 expression and the genetic deficiency in the shiverer mouse myelination mutant (12,34,44). Several groups have recently isolated cDNA ...

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

Characterization of myelin proteolipid mRNAs in normal and jimpy mice.

Gardinier¹,

Macklin²,

Diniak³

et al. 1986

Mol. Cell. Biol.

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“…PLP is remarkably well conserved among mouse (this report), rat (1,16), cow (2), and human (C.P., L.D.H., and R.A.L., unpublished work) at the amino acid and nucleotide level. The protein encoded by the mouse PLP cDNA (Fig.…”

Section: Resultsmentioning

confidence: 69%

“…The protein encoded by the mouse PLP cDNA (Fig. 1) is identical to the rat (16) and human (C.P., L.D.H., and R.A.L., unpublished work) PLP and displays only two conservative amino acid differences from the bovine sequence (2 (18) or dideoxy chain termination (19) methods. The most 5' 300 bases of phage A PLP2, which extends from position one to the secondary polyadenylylation site at 2288, were also sequenced.…”

Section: Resultsmentioning

confidence: 91%

Aberrant splicing of proteolipid protein mRNA in the dysmyelinating jimpy mutant mouse.

Hudson¹,

Berndt²,

Puckett³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

171

113

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ABSTRACTcDNA clones encoding proteolipid protein (PLP) were isolated from a mouse brain library and sequenced. We describe two transcripts arising from the PLP locus by alternative splicing: the major one encodes the 277-amino acid PLP protein and the minor one corresponds to the DM-20 protein, a PLP-like protein of 20,000 Mr that shares both amino and carboxyl regions with PLP. These two transcripts lack -70 bases in PLP mRNA from the dysmyelinating jimpy mutant. The deletion spans amino acids 208-232; however, this region is present in thejimpy PLP-encoding gene. We propose that the jimpy mutant suffers a point mutation or the deletion of a few bases in the PLP gene that alters the normal splicing pattern and generates partially deleted PLP transcripts. RESULTS AND DISCUSSIONConservation of PLP Sequence. PLP is remarkably well conserved among mouse (this report), rat (1, 16), cow (2), and human (C.P., L.D.H., and R.A.L., unpublished work) at the amino acid and nucleotide level. The protein encoded by the mouse PLP cDNA (Fig. 1) is identical to the rat (16) and human (C.P., L.D.H., and R.A.L., unpublished work) PLP and displays only two conservative amino acid differences from the bovine sequence (2). The striking degree of conserAbbreviations: PLP, proteolipid protein; MBP, myelin basic protein.

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“…This modification most commonly occurs on cysteines (see, for review, Refs. 39, 45, and 46), although it has also been found on serine (47), threonine (48), and lysine residues (49). The cysteine residues in the cytoplasmic domain of TGF-␣ are potential sites of this type of lipid modification of transmembrane TGF-␣.…”

mentioning

confidence: 98%

Cysteines 153 and 154 of Transmembrane Transforming Growth Factor-α Are Palmitoylated and Mediate Cytoplasmic Protein Association

Shum

Turck

Derynck

1996

Journal of Biological Chemistry

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Transforming growth factor-␣ (TGF-␣) is synthesized as a transmembrane protein with a highly conserved, short cytoplasmic domain that is rich in cysteines. TGF-␣ is a prototype of a large family of growth factors involved in cell-cell communication. We have shown previously that transmembrane TGF-␣ associates with a kinase activity and two proteins of 106 and 86 kDa. In this study, we have used site-directed mutagenesis of the cytoplasmic domain of TGF-␣ to define the structural requirements for these protein interactions. Whereas the cytoplasmic domain of TGF-␣ was not essential for association with transmembrane p106, deletion of the C-terminal 8 amino acids, including a cysteine pair, abolished the interaction with p86 and greatly reduced the kinase activity associated with transmembrane TGF-␣. Replacement of these 2 cysteines by serines similarly reduced the association of p86 with transmembrane TGF-␣. Using a combination of mutational analysis and direct microsequencing, we have determined that this cysteine pair was palmitoylated. We therefore conclude that these cysteines play a critical role in the interaction of TGF-␣ with associated proteins and in the function of this protein complex. The palmitoylation of these cysteines suggests a possibly dynamic role of fatty acid modification in the integrity and function of the transmembrane TGF-␣ complex.

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Molecular cloning and nucleotide sequence of a cDNA clone coding for rat brain myelin proteolipid

Cited by 60 publications

References 17 publications

Characterization of myelin proteolipid mRNAs in normal and jimpy mice.

Characterization of myelin proteolipid mRNAs in normal and jimpy mice.

Aberrant splicing of proteolipid protein mRNA in the dysmyelinating jimpy mutant mouse.

Cysteines 153 and 154 of Transmembrane Transforming Growth Factor-α Are Palmitoylated and Mediate Cytoplasmic Protein Association

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