Proteolipid protein 1 explained

Proteolipid protein 1 (PLP1) is a form of myelin proteolipid protein (PLP). Mutations in PLP1 are associated with Pelizaeus–Merzbacher disease. It is a 4 transmembrane domain protein which is proposed to bind other copies of itself on the extracellular side of the membrane. In a myelin sheath, as the layers of myelin wraps come together, PLP will bind itself and tightly hold the cellular membranes together.

This gene encodes a transmembrane proteolipid protein that is the predominant myelin protein present in the central nervous system (CNS). The encoded protein functions in myelination. This protein may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations associated with this gene cause X-linked Pelizaeus–Merzbacher disease and spastic paraplegia type 2. Two transcript variants encoding distinct isoforms have been identified for this gene.^[1]

In melanocytic cells PLP1 gene expression may be regulated by MITF.^[2]

Interactions

Proteolipid protein 1 has been shown to interact with Myelin basic protein.^{[3] [4]}

See also

• PLP2

Further reading

• Woodward K, Malcolm S . Proteolipid protein gene: Pelizaeus-Merzbacher disease in humans and neurodegeneration in mice. . Trends Genet. . 15 . 4 . 125–8 . 1999 . 10203813 . 10.1016/S0168-9525(99)01716-3 .
• Garbern J, Cambi F, Shy M, Kamholz J . The molecular pathogenesis of Pelizaeus-Merzbacher disease. . Arch. Neurol. . 56 . 10 . 1210–4 . 1999 . 10520936 . 10.1001/archneur.56.10.1210 . free .
• Yool DA, Edgar JM, Montague P, Malcolm S . The proteolipid protein gene and myelin disorders in man and animal models. . Hum. Mol. Genet. . 9 . 6 . 987–92 . 2000 . 10767322 . 10.1093/hmg/9.6.987 . free .
• Hudson LD . Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene. . J. Child Neurol. . 18 . 9 . 616–24 . 2003 . 14572140 . 10.1177/08830738030180090801 . 38917872 .
• Inoue K . PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. . Neurogenetics . 6 . 1 . 1–16 . 2005 . 15627202 . 10.1007/s10048-004-0207-y . 32631043 .
• Doll R, Natowicz MR, Schiffmann R, Smith FI . Molecular diagnostics for myelin proteolipid protein gene mutations in Pelizaeus-Merzbacher disease . Am. J. Hum. Genet. . 51 . 1 . 161–9 . 1992 . 1376966 . 1682866 .
• Strautnieks S, Rutland P, Winter RM, etal . Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis . Am. J. Hum. Genet. . 51 . 4 . 871–8 . 1992 . 1384324 . 1682779 .
• Pratt VM, Trofatter JA, Schinzel A, etal . A new mutation in the proteolipid protein (PLP) gene in a German family with Pelizaeus-Merzbacher disease . Am. J. Med. Genet. . 38 . 1 . 136–9 . 1991 . 1707231 . 10.1002/ajmg.1320380129 .
• Weimbs T, Dick T, Stoffel W, Boltshauser E . A point mutation at the X-chromosomal proteolipid protein locus in Pelizaeus-Merzbacher disease leads to disruption of myelinogenesis . Biol. Chem. Hoppe-Seyler . 371 . 12 . 1175–83 . 1991 . 1708672 . 10.1515/bchm3.1990.371.2.1175.
• Popot JL, Pham Dinh D, Dautigny A . Major Myelin proteolipid: the 4-alpha-helix topology . J. Membr. Biol. . 120 . 3 . 233–46 . 1991 . 1711121 . 10.1007/BF01868534 . 24450880 .
• Pham-Dinh D, Popot JL, Boespflug-Tanguy O, etal . Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid . Proc. Natl. Acad. Sci. U.S.A. . 88 . 17 . 7562–6 . 1991 . 1715570 . 10.1073/pnas.88.17.7562 . 52341 . 1991PNAS...88.7562P . free .
• Simons R, Alon N, Riordan JR . Human myelin DM-20 proteolipid protein deletion defined by cDNA sequence . Biochem. Biophys. Res. Commun. . 146 . 2 . 666–71 . 1987 . 2441695 . 10.1016/0006-291X(87)90580-8 .
• Kronquist KE, Crandall BF, Macklin WB, Campagnoni AT . Expression of myelin proteins in the developing human spinal cord: cloning and sequencing of human proteolipid protein cDNA . J. Neurosci. Res. . 18 . 3 . 395–401 . 1988 . 2449536 . 10.1002/jnr.490180303 . 4367384 .
• Edwards AM, Ross NW, Ulmer JB, Braun PE . Interaction of myelin basic protein and proteolipid protein . J. Neurosci. Res. . 22 . 1 . 97–102 . 1989 . 2467009 . 10.1002/jnr.490220113 . 33666906 .
• Hudson LD, Puckett C, Berndt J, etal . Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder . Proc. Natl. Acad. Sci. U.S.A. . 86 . 20 . 8128–31 . 1989 . 2479017 . 10.1073/pnas.86.20.8128 . 298228 . 1989PNAS...86.8128H . free .
• Trofatter JA, Dlouhy SR, DeMyer W, etal . Pelizaeus-Merzbacher disease: tight linkage to proteolipid protein gene exon variant . Proc. Natl. Acad. Sci. U.S.A. . 86 . 23 . 9427–30 . 1990 . 2480601 . 10.1073/pnas.86.23.9427 . 298509 . 1989PNAS...86.9427T . free .
• Gencic S, Abuelo D, Ambler M, Hudson LD . Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein . Am. J. Hum. Genet. . 45 . 3 . 435–42 . 1989 . 2773936 . 1683421 .
• Mattei MG, Alliel PM, Dautigny A, etal . The gene encoding for the major brain proteolipid (PLP) maps on the q-22 band of the human X chromosome . Hum. Genet. . 72 . 4 . 352–3 . 1986 . 3457761 . 10.1007/BF00290964 . 35833817 .
• Diehl HJ, Schaich M, Budzinski RM, Stoffel W . Individual exons encode the integral membrane domains of human myelin proteolipid protein . Proc. Natl. Acad. Sci. U.S.A. . 83 . 24 . 9807–11 . 1987 . 3467339 . 10.1073/pnas.83.24.9807 . 387231 . 1986PNAS...83.9807D . free .
• Kahan I, Moscarello MA . The intramembranous domains of lipophilin in phosphatidylcholine vesicles are similar to those in the myelin membrane . Biochim. Biophys. Acta . 862 . 1 . 223–6 . 1986 . 3768366 . 10.1016/0005-2736(86)90487-6 .

External links

• • GeneReview/NCBI/NIH/UW entry on PLP1-Related Disorders

Notes and References

1. Web site: Entrez Gene: PLP1 proteolipid protein 1 (Pelizaeus-Merzbacher disease, spastic paraplegia 2, uncomplicated).
2. Hoek KS, Schlegel NC, Eichhoff OM, etal . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell Melanoma Res. . 21 . 6 . 665–76 . 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . free .
3. Wood . D D . Vella G J . Moscarello M A . Oct 1984 . Interaction between human myelin basic protein and lipophilin . Neurochem. Res. . 9 . 10 . 1523–31 . UNITED STATES. 0364-3190. 6083474 . 10.1007/BF00964678 . 9751765 .
4. Edwards . A M . Ross N W . Ulmer J B . Braun P E . Jan 1989 . Interaction of myelin basic protein and proteolipid protein . J. Neurosci. Res. . 22 . 1 . 97–102 . UNITED STATES. 0360-4012. 2467009 . 10.1002/jnr.490220113 . 33666906 .