Proteolipid plasmolipin: localization in polarized cells, regulated expression and lipid raft association in CNS and PNS myelin

Bosse, Frank; Hasse, Birgit; Pippirs, U.; Greiner–Petter, Regine; Müller, Hans‐Werner

doi:10.1046/j.1471-4159.2003.01870.x

Cited by 37 publications

(42 citation statements)

References 49 publications

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“…Although CLDN14 and clarin-1 are expressed in hair cells, they are localized to the basolateral membranes of these cells. TMHS is the only tetraspan protein known to localize to the apical membrane and stereocilia of hair cells, although other tetraspan proteins have been localized to the apical membranes of polarized epithelial cells in other tissues (30,31).…”

Section: Discussionmentioning

confidence: 99%

A missense mutation in the previously undescribed geneTmhsunderlies deafness in hurry-scurry (hscy) mice

Longo-Guess

Gagnon

Cook

et al. 2005

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

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Mouse deafness mutations provide valuable models of human hearing disorders and entry points into molecular pathways important to the hearing process. A newly discovered mouse mutation named hurry-scurry (hscy) causes deafness and vestibular dysfunction. Scanning electron microscopy of cochleae from 8-dayold mutants revealed disorganized hair bundles, and by 50 days of age, many hair cells are missing. To positionally clone hscy, 1,160 F 2 mice were produced from an intercross of (C57BL͞6-hscy ؋ CAST͞EiJ) F 1 hybrids, and the mutation was localized to a 182-kb region of chromosome 17. A missense mutation causing a critical cysteine to phenylalanine codon change was discovered in a previously undescribed gene within this candidate interval. The gene is predicted to encode an integral membrane protein with four transmembrane helices. A synthetic peptide designed from the predicted protein was used to produce specific polyclonal antibodies, and strong immunoreactivity was observed on hair bundles of both inner and outer hair cells in cochleae of newborn ؉͞؉ controls and ؉͞hscy heterozygotes but was absent in hscy͞ hscy mutants. Accordingly, the gene was given the name ''tetraspan membrane protein of hair cell stereocilia,'' symbol Tmhs. Two related proteins (>60% amino acid identity) are encoded by genes on mouse chromosomes 5 and 6 and, together with the Tmhsencoded protein (TMHS), comprise a distinct tetraspan subfamily. Our localization of TMHS to the apical membrane of inner ear hair cells during the period of stereocilia formation suggests a function in hair bundle morphogenesis.mouse ͉ hair cell ͉ stereocilia ͉ tetraspan H earing loss is the most prevalent sensory disorder in human populations, occurring in Ϸ0.2-0.3% of all live births. More than half of these childhood cases are thought to be genetic (1). The development and maintenance of the intricate structures and complex mechanisms of the mammalian inner ear require the proper functioning and concerted interactions of hundreds of genes and their products. To date, Ͼ100 forms of human nonsyndromic deafness have been genetically mapped (Hereditary Hearing Loss Homepage (http:͞͞dnalab-www.uia.ac.be͞ dnalab͞hhh), and many of the genes responsible have been identified and characterized (2). More than 200 mouse mutations are known to affect hearing and balance, and mouse models have been developed for Ͼ50 human hearing disorders (Hearing Impairment in Mice, www.jax.org͞hmr͞index.html). Because of the complex nature of the ear, it is likely that many more deafness-related genes remain to be discovered.The inner ear is comprised of the vestibular region, which controls balance, and the cochlea, which is important in detecting, amplifying, and transmitting auditory information to the brain. In the organ of Corti of the cochlea, two distinct types of sensory cells, inner and outer hair cells, are essential for the transduction of sound into nerve impulses. Stereocilia are modified microvilli that project from the apical membranes of inner ear hair cells. The acti...

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Section: Discussionmentioning

confidence: 99%

A missense mutation in the previously undescribed geneTmhsunderlies deafness in hurry-scurry (hscy) mice

Longo-Guess

Gagnon

Cook

et al. 2005

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

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“…S1). Plasmolipin localizes mainly to the sphingolipid and cholesterol enriches myelin membranes as well as the apical membranes in epithelia (Bosse et al, 2003). Although the molecular model of plasmolipin showed a different helix organization (supplementary material Fig.…”

Section: Bioinformatics Analysis and Structure Prediction Of Ocln Marvelmentioning

confidence: 99%

The MARVEL transmembrane motif of occludin mediates oligomerization and targeting to the basolateral surface in epithelia

Yaffe

Shepshelovitch

Nevo-Yassaf

et al. 2012

Journal of Cell Science

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SummaryOccludin (Ocln), a MARVEL-motif-containing protein, is found in all tight junctions. MARVEL motifs are comprised of four transmembrane helices associated with the localization to or formation of diverse membrane subdomains by interacting with the proximal lipid environment. The functions of the Ocln MARVEL motif are unknown. Bioinformatics sequence-and structure-based analyses demonstrated that the MARVEL domain of Ocln family proteins has distinct evolutionarily conserved sequence features that are consistent with its basolateral membrane localization. Live-cell microscopy, fluorescence resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) were used to analyze the intracellular distribution and self-association of fluorescentprotein-tagged full-length human Ocln or the Ocln MARVEL motif excluding the cytosolic C-and N-termini (amino acids 60-269, FP-MARVEL-Ocln). FP-MARVEL-Ocln efficiently arrived at the plasma membrane (PM) and was sorted to the basolateral PM in filtergrown polarized MDCK cells. A series of conserved aromatic amino acids within the MARVEL domain were found to be associated with Ocln dimerization using BiFC. FP-MARVEL-Ocln inhibited membrane pore growth during Triton-X-100-induced solubilization and was shown to increase the membrane-ordered state using Laurdan, a lipid dye. These data demonstrate that the Ocln MARVEL domain mediates self-association and correct sorting to the basolateral membrane.

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“…PLLP is a major component of myelin (4,10), is present in the apical membranes of tubular epithelial cells, and has been detected in a variety of other tissues (3,15). PLLP can be extracted from membranes using organic solvents and, upon its addition to synthetic lipid bilayers, can induce the formation of ion channels that are both voltage dependent and potassium specific (43).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Myelin Protein Plasmolipin as the Cell Entry Receptor forMus caroliEndogenous Retrovirus

Miller

Bergholz

Ziegler

et al. 2008

J Virol

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The Asian wild mouse species Mus caroli harbors an endogenous retrovirus (McERV) that is closely related to but distinct from the endogenous retrovirus family defined by the Mus dunni endogenous virus and the Mus musculus endogenous retrovirus. McERV could infect some cell types from humans, dogs, and rats, but not all, and did not infect any mouse cell line tested. Because of its interesting host range and proposed ancestral relationship to primate retroviruses and because none of the entry receptors for this family of retroviruses had been identified, we began a search for the McERV receptor. We determined the chromosomal location of the receptor gene in the human genome by phenotypic screening of the G3 human-hamster radiation hybrid cell line panel and confirmed the localization by assaying for receptor activity conferred by bacterial artificial chromosome (BAC) clones spanning the region. We next localized the gene more precisely in one positive BAC by assaying for receptor activity following BAC digestion with several restriction enzymes that cleaved different sets of genes, and we confirmed that the final candidate gene, plasmolipin (PLLP; TM4SF11), is the novel receptor by showing that the expression of the human PLLP cDNA renders hamster and mouse cells susceptible to McERV infection. PLLP functions as a voltage-dependent potassium ion channel and is expressed primarily in kidney and brain, helping to explain the limited range of cell types that McERV can infect. Interestingly, mouse PLLP also functioned well as a receptor for McERV but was simply not expressed in the mouse cell types that we originally tested.An endogenous gammaretrovirus can be induced from cells of the Asian wild mouse Mus caroli by treatment of the cells with bromodeoxyuridine (22). This virus is distinct from the murine leukemia virus (MuLV) family of active retroviruses found in the laboratory mouse Mus musculus and appeared to be similar to exogenous retroviruses from gibbon apes (gibbon ape leukemia virus [GALV]) and woolly monkeys (simian sarcoma-associated virus [SSAV]). These similarities included a xenotropic host range (the ability to infect cells from species other than mice but not cells from mice) and reported cross interference between the viruses, indicative of a common cell entry receptor. It was therefore hypothesized that mice were the source of the exogenous simian viruses. Recently, a retrovirus induced by bromodeoxyuridine treatment of Mus caroli (Mus caroli endogenous retrovirus [McERV]) that has properties similar to those of the original virus studied over 30 years ago (22) was cloned and sequenced (C. Stocking, M. Ziegler, U. Bergholz, K. Weber, M. Eiden, and V. Prassolov, unpublished results). However, further analysis indicated that McERV does not use the cell entry receptor used by GALV and SSAV (Pit1; Slc20a1), weakening the argument that McERV is the progenitor of GALV and/or SSAV. McERV also did not use the receptors for xenotropic MuLV (Xpr1) (Mus musculus) or those for the endogenous feline leukemia v...

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Proteolipid plasmolipin: localization in polarized cells, regulated expression and lipid raft association in CNS and PNS myelin

Cited by 37 publications

References 49 publications

A missense mutation in the previously undescribed geneTmhsunderlies deafness in hurry-scurry (hscy) mice

A missense mutation in the previously undescribed geneTmhsunderlies deafness in hurry-scurry (hscy) mice

The MARVEL transmembrane motif of occludin mediates oligomerization and targeting to the basolateral surface in epithelia

Identification of the Myelin Protein Plasmolipin as the Cell Entry Receptor forMus caroliEndogenous Retrovirus

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