Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes

Feldmann, Anke; Winterstein, Christine; White, Robin; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

doi:10.1002/jnr.22020

Cited by 41 publications

(76 citation statements)

References 45 publications

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“…We previously analyzed the SNARE expression profile in oligodendroglial cells, which appeared identical in the cell line Oli-neu and primary oligodendrocytes (Feldmann et al, 2009). VAMP3 localized to the RE and its mRNA expression and protein levels were upregulated during differentiation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For the interaction to occur, it was essential to coexpress both partners in the same cell. On mixing of individually transfected cells before cell lysis, the interaction between VAMP3 and Stx4 or VAMP3 and Stx3 was not detectable demonstrating that the interaction had to occur in a living cell and did not result from the solubilization procedure (data not shown) (Feldmann et al, 2009). These results underscore that, even on overexpression in oligodendroglial cells, VAMP3 exhibits specificity toward interaction with Stx4, whereas VAMP7 specifically interacts with Stx3.…”

Section: Syntaxin-3 and -4 Are Putative Cognate Target Q-snaresmentioning

confidence: 91%

“…Oli-neu cells were cotransfected with pEGFP-C3-cellubrevin or pEGFP-C3-TI-VAMP and either pcDNA/TO/mycHisA-Stx2, -Stx3, or -Stx4 expression vectors, and immunoprecipitation (IP) was performed 24 h later as described previously (Feldmann et al, 2009). Briefly, cells were pretreated for 15 min with 1 mM N-ethylmaleimide in PBS and scraped in 1 ml of lysis buffer (1% Triton X-100, 50 mM Tris, pH 7.4, 150 mM NaCl, 1 g/ml aprotinin, 5 g/ml leupeptin, 1 g/ml pepstatin, 1 mM PMSF, and 1 mM N-ethylmaleimide).…”

Section: Methodsmentioning

confidence: 99%

“…Putative plasma membrane target SNAREs of VAMP3 and VAMP7 may be the Q a -SNAREs Stx2, Stx3, Stx4, and the Q bc -SNARE SNAP23, which all are expressed by oligodendrocytes and localize to the myelin membrane (Feldmann et al, 2009). To identify the Q a receptors of VAMP3 and VAMP7 controlling PLP surface transport, we coexpressed myc-tagged Stx2, Stx3, or Stx4 with PLP in Oli-neu cells.…”

Section: Syntaxin-3 and -4 Are Putative Cognate Target Q-snaresmentioning

confidence: 99%

“…To identify SNAREs mediating fusion in myelin membrane traffic, we initially performed a systematic analysis of oligodendroglial SNARE expression, localization, and putative complex formation facilitating the choice of individual SNAREs for functional analyses (Feldmann et al, 2009). Here, we explore the functional involvement of the R-SNAREs VAMP3 [cellubrevin (McMahon et al, 1993)] and VAMP7 [tetanus neurotoxininsensitive (TI)-VAMP (Galli et al, 1998)] in myelin membrane trafficking in vitro and in vivo focusing on transport of the major myelin protein PLP.…”

Section: Introductionmentioning

confidence: 99%

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Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Feldmann¹,

Amphornrat²,

Schönherr³

et al. 2011

J. Neurosci.

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CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominantnegative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myelination defects. Interestingly, AP-3␦-deficient mocha mice, which suffer from impaired secretion of lysosome-related organelles and missorting of VAMP7, exhibit a mild dysmyelination characterized by reduced levels of select myelin proteins, including PLP. We conclude that PLP reaches the cell surface via at least two trafficking pathways with distinct regulations: (1) VAMP3 mediates fusion of recycling endosomederived vesicles with the oligodendroglial plasma membrane in the course of the secretory pathway; (2) VAMP7 controls exocytosis of PLP from late endosomal/lysosomal organelles as part of a transcytosis pathway. Our in vivo data suggest that exocytosis of lysosomerelated organelles controlled by VAMP7 contributes to myelin biogenesis by delivering cargo to the myelin membrane.

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Section: Resultsmentioning

confidence: 99%

Section: Syntaxin-3 and -4 Are Putative Cognate Target Q-snaresmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Syntaxin-3 and -4 Are Putative Cognate Target Q-snaresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Feldmann¹,

Amphornrat²,

Schönherr³

et al. 2011

J. Neurosci.

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A critical role for the cholesterol‐associated proteolipids PLP and M6B in myelination of the central nervous system

Werner

Krämer-Albers

Strenzke

et al. 2013

Glia

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103

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The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport.

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Unconventional myosin ID is expressed in myelinating oligodendrocytes

Yamazaki

Ishibashi

Baba

et al. 2014

J of Neuroscience Research

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Myelin is a dynamic multilamellar structure that ensheathes axons and is crucial for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes that wrap many layers of plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we found that myosin ID (Myo1d), a class I myosin, is enriched in the rat CNS myelin fraction. Myo1d is an unconventional myosin and has been shown to be involved in membrane trafficking in the recycling pathway in an epithelial cell line. Western blotting revealed that Myo1d expression begins early in myelinogenesis and continues to increase into adulthood. The localization of Myo1d in CNS myelin has not been reported, and the function of Myo1d in vivo remains unknown. To demonstrate the expression of Myo1d in CNS myelin and to begin to explore the function of Myo1d in myelination, we produced a new antibody against Myo1d that has a high titer and specificity for rat Myo1d. By using this antibody, we demonstrated that Myo1d is expressed in rat CNS myelin and is especially abundant in abaxonal and adaxonal regions (the outer and inner cytoplasm-containing loops, respectively), but that expression is low in peripheral nervous system myelin. In culture, Myo1d was expressed in mature rat oligodendrocytes. Furthermore, an increase in expression of Myo1d during maturation of CNS white matter (cerebellum and corpus callosum) was demonstrated by histological analysis. These results suggest that Myo1d may be involved in the formation and/or maintenance of CNS myelin.

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Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes

Cited by 41 publications

References 45 publications

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

A critical role for the cholesterol‐associated proteolipids PLP and M6B in myelination of the central nervous system

Unconventional myosin ID is expressed in myelinating oligodendrocytes

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