A proteolipid protein gene family: Expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide

Kitagawa, Kazuo; Sinoway, M. P.; Yang, Chun; Gould, Robert M.; Colman, David

doi:10.1016/0896-6273(93)90148-k

Cited by 156 publications

(151 citation statements)

References 64 publications

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“…An acidified endosome is important for the recycling of internalized receptors [32,33]. In support of this hypothesis, tetraspan proteolipids, including members of the PLP family, are known to contribute to the formation of pore structures in a wide spectrum of cellular systems [38]. Moreover, Rhombex-29, a new member of the PLP family, was suggested to be responsible for transporting H + [39].…”

Section: Discussionmentioning

confidence: 83%

Membrane glycoprotein M6A promotes μ-opioid receptor endocytosis and facilitates receptor sorting into the recycling pathway

Liang

Stumm

et al. 2008

Cell Res

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The interaction of μ-opioid receptor (MOPr) with the neuronal membrane glycoprotein M6a is known to facilitate MOPr endocytosis in human embryonic kidney 293 (HEK293) cells. To further study the role of M6a in the post-endocytotic sorting of MOPr, we investigated the agonist-induced co-internalization of MOPr and M6a and protein targeting after internalization in HEK293 cells that co-expressed HA-tagged MOPr and Myc-tagged M6a. We found that M6a, MOPr, and Rab 11, a marker for recycling endosomes, co-localized in endocytotic vesicles, indicating that MOPr and M6a are primarily targeted to recycling endosomes after endocytosis. Furthermore, co-expression of M6a augmented the post-endocytotic sorting of δ-opioid receptors into the recycling pathway, indicating that M6a might have a more general role in opioid receptor post-endocytotic sorting. The enhanced post-endocytotic sorting of MOPr into the recycling pathway was accompanied by a decrease in agonist-induced receptor down-regulation of M6a in co-expressing cells. We tested the physiological relevance of these findings in primary cultures of cortical neurons and found that co-expression of M6a markedly increased the translocation of MOPrs from the plasma membrane to intracellular vesicles at steady state and significantly enhanced both constitutive and agonist-induced receptor endocytosis. In conclusion, our results strongly indicate that M6a modulates MOPr endocytosis and post-endocytotic sorting and has an important role in receptor regulation.

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Section: Discussionmentioning

confidence: 83%

Membrane glycoprotein M6A promotes μ-opioid receptor endocytosis and facilitates receptor sorting into the recycling pathway

Liang

Stumm

et al. 2008

Cell Res

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“…The human DM20 amino acid sequence was compared with those of the DM20 of trout 14 and chicken, 15 the M6a, M6b proteins of humans 16 and mice 17 and the squalus DMα, DM and DMγ proteins. 18 Dark blue circles indicate highly conserved amino acids (90 to 100% identity), sky blue circles indicate partially conserved amino acids (60 to 89% identity) and white circles, non-conserved amino acids ( < 60% identity). The 23 missense mutations found are represented as circles.…”

Section: Discussionmentioning

confidence: 99%

“…18 Amino acids 90 to 100% identical were considered to be highly conserved, those 60-89% identical, partially conserved and those less than 60% identical, not conserved.…”

Section: Amino-acid Sequence Comparison For Dm Proteinsmentioning

confidence: 99%

Genotype–phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations

et al. 2000

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Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2) are X-linked developmental defects of myelin formation affecting the central nervous system (CNS). They differ clinically in the onset and severity of the motor disability but both are allelic to the proteolipid protein gene (PLP), which encodes the principal protein components of CNS myelin, PLP and its spliced isoform, DM20. We investigated 52 PMD and 28 SPG families without large PLP duplications or deletions by genomic PCR amplification and sequencing of the PLP gene. We identified 29 and 4 abnormalities respectively. Patients with PLP mutations presented a large range of disease severity, with a continuum between severe forms of PMD, without motor development, to pure forms of SPG. Clinical severity was found to be correlated with the nature of the mutation, suggesting a distinct strategy for detection of PLP point mutations between severe PMD, mild PMD and SPG. Single amino-acid changes in highly conserved regions of the DM20 protein caused the most severe forms of PMD. Substitutions of less conserved amino acids, truncations, absence of the protein and PLP-specific mutations caused the milder forms of PMD and SPG. Therefore, the interactions and stability of the mutated proteins has a major effect on the severity of PLP-related diseases.

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“…These observations imply evolutionary acquisition of new protein functions (Aharoni et al, 2005), which appears to have been the evolutionary progression of the pgf proteins among marine and terrestrial vertebrates (Kitagawa et al, 1993). James et al (2003) have suggested that conformational diversity, i.e., one sequence adopting multiple structures and functions, as in the conserved sequences among pgf proteins, can increase the numbers of potential antibody targets, thereby enhancing the likelihood of developing cross-reactivity, which can result in autoimmunity (Cohn, 2005).…”

Section: Mab Recognition Of Neuronsmentioning

confidence: 99%

“…The DM protein members of the PLP/ DM-20 gene family (pgf; also referred to as ''lipophilins''; Gow, 1997) are found in CNS myelin in bony fish and sharks, but they exhibit greater sequence diversity, suggesting their greater plasticity (Kitagawa et al, 1993;Geltner et al, 1998). Members of the pgf are also expressed in nonmyelinating cells, including neurons, in developing and mature vertebrate CNS tissues (Kitagawa et al, 1993;Yan et al, 1993Yan et al, , 1996Roussel et al, 1998;Werner et al, 2001;Jacobs et al, 2003Jacobs et al, , 2004. To our knowledge, however, evolutionary conservation of pgf protein epitopes in situ has not been investigated.…”

mentioning

confidence: 99%

Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species

Greenfield¹,

Reddy²,

Lees³

et al. 2006

J of Neuroscience Research

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Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50–69, 100–123, 139–151, 178–191, 200–219, 264–276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti‐100–123 mAb did not recognize DM‐20, the PLP isoform that lacks residues 116–150. All of the mAbs stained fixed, permeabilized oligodendrocytes and mammalian and avian CNS tissue myelin. Most of the mAbs also stained amphibian, teleost, and elasmobranch CNS myelin despite greater diversity of their pgf myelin protein sequences. Myelin staining was observed when there was at least 40% identity of the mAb epitope and known pgf myelin proteins of the same or related species. The pgf myelin proteins of teleosts and elasmobranchs lack 116–150; the anti‐100–123 mAb did not stain their myelin. In addition to myelin, the anti‐178–191 mAb stained many neurons in all species; other mAbs stained distinct neuron subpopulations in different species. Neuronal staining was observed when there was at least approximately 30% identity of the PLP mAb epitope and known pgf neuronal proteins of the same or related species. Thus, anti‐human PLP epitope mAbs simultaneously recognize CNS myelin and neurons even without extensive sequence identity. Widespread anti‐PLP mAb recognition of neurons suggests a novel potential pathophysiologic mechanism in MS patients, i.e., that anti‐PLP antibodies associated with demyelination might simultaneously recognize pgf epitopes in neurons, thereby affecting their functions. © 2006 Wiley‐Liss, Inc.

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A proteolipid protein gene family: Expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide

Cited by 156 publications

References 64 publications

Membrane glycoprotein M6A promotes μ-opioid receptor endocytosis and facilitates receptor sorting into the recycling pathway

Membrane glycoprotein M6A promotes μ-opioid receptor endocytosis and facilitates receptor sorting into the recycling pathway

Genotype–phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations

Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species

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