Identification of GTP‐ binding proteins in myelin and oligodendrocyte membranes

Braun, Peter E.; Horvath, E.; Yong, V. Wee; Bernier, Lise

doi:10.1002/jnr.490260103

Cited by 45 publications

(29 citation statements)

References 35 publications

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“…Ras and other GTP-binding proteins have been found in purified myelin membranes and membrane fractions from cultured oligodendrocytes. Developmentally, ras was highest in myelin from 1 I-day-old animals, but was present in myelin at all ages from 11 days to adult (Braun et al, 1990). It is interesting to note that during development, an increase in Gap111 mRNA was found around postnatal days 12-15 (Fig.…”

Section: Discussionmentioning

confidence: 92%

GapIII, a new brain‐enriched member of the GTPase‐activating protein family

Baba

Fuss

Urano

et al. 1995

J of Neuroscience Research

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Ras GTPase-activating proteins (GAPs) are negative regulators of ras, which controls proliferation and differentiation in many cells. Ras GAPs have been found in a variety of species from yeast to mammals. We describe here a newly identified mammalian GAP, GapIII, which was obtained by differential screening of a rat oligodendrocyte cDNA library. GapIII putatively encodes a 834 amino acid protein with a predicted molecular weight of 96 kDa, which contains a consensus GAP-related domain (GRD). The protein encoded by this cDNA has high homology with Gap1m, which was recently identified as a putative mammalian homolog of Drosophila Gap1. These proteins contain three structural domains, an N-terminal calcium-dependent phospholipid binding domain, GRD, and a C-terminal PH/Btk domain. Because of the sequence homology and the structural similarities of this protein with Gap1m, we hypothesize that GapIII and Gap1m may be members of a mammalian GAP gene family, separate from p120GAP, neurofibromin (NF1), and IQGAP. To confirm the GapIII protein activity, constructs containing different GapIII-GRD domains were transformed into iral mutant yeast to determine their relative ability to replace IRA1 functionally. Constructs that contained essentially the full-length protein (all three domains), the GRD alone, or the GRD plus PH/Btk domain suppressed heat shock sensitivity of ira1, whereas constructs that contained the GRD with part of the PH/Btk domain had only a weak ability to suppress heat shock sensitivity. These results suggest that the GapIII GRD itself is sufficient to down-regulate ras proteins in yeast. Expression of GapIII mRNA (4.2 kb) was examined by Northern analysis and in situ hybridization. This mRNA was expressed at highest levels in the brain, where its expression increased with development. Lower levels of the mRNA were expressed in the spleen and lung. Among neural cells, GapIII mRNA was expressed in neurons and oligodendrocytes, but not in astrocytes. Interestingly, the expression pattern in brain is reminiscent of type 1 NF1 expression reported by Gutmann et al. (Cell Growth Differ in press, 1995). We propose that in addition to p120GAP and neurofibromin, the GapIII/Gap1m family may be important for modulating ras activity in neurons and oligodendrocytes during normal brain development and in particular in the adult brain.

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Section: Discussionmentioning

confidence: 92%

GapIII, a new brain‐enriched member of the GTPase‐activating protein family

Baba

Fuss

Urano

et al. 1995

J of Neuroscience Research

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“…The existence of diverse mechanisms involved in the regulation of MBP phosphorylation underscores its significance in signal transduction in OLGs and myelin. Heterotrimeric GTP binding proteins, ras protein, and other low molecular weight GTP-binding proteins have been detected in myelin (Braun et al, 1990;Larocca et al, 1991;Huber et al, 1994). MBP phosphorylation is differentially modulated by PKC and PKA (Vartanian et al, 1986;Ulmer, 1988), is decreased during hypoxia (Qi and Dawson, 1993), is increased by impulse conduction in optic nerves (Murray and Steck, 1984), and is decreased by endogenous myelin phosphatase (Yang et al, 1987).…”

Section: Discussionmentioning

confidence: 98%

Arachidonic acid inhibits myelin basic protein phosphorylation in cultured oligodendrocytes

Takeda

Soliven

1997

Glia

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“…Indeed, signaling molecules, such as Fyn tyrosine kinase, have been identified in the cytoplasmic channels surrounding MBP domains in the sheets (Osterhout et al, 1999). Another likely candidate signaling molecule is CNPase because it binds GTP, is isoprenylated, is colocalized along the cytoskeleton, and it markedly affects cellular morphology when transfected into CNPasedeficient cells (Braun et al, 1990;De Angelis andBraun, 1994, 1996). It may be that cholesterol interacts with signaling proteins in membrane sheets, because cholesterol covalently binds to the signal transduction protein sonic hedgehog protein (Shh) in embryonic tissue.…”

Section: Redistributed Cholesterol Directly Overlies Veinlike Structumentioning

confidence: 96%

Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways

Lintner

Dyer

2000

J. Neurosci. Res.

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Cultured oligodendrocytes produce extensive membrane sheets that contain an internal lacy network of vein-like structures composed of microtubules, actin filaments, and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase). These cytoplasmic vein-like structures surround domains of myelin basic protein (MBP). Using the antibiotic filipin, that binds to cholesterol, the relationship between plasma membrane cholesterol and cytoskeleton in membrane sheets was examined. Our results show that cholesterol was relatively uniformly distributed within the plasma membranes of prefixed control oligodendrocyte membrane sheets. When live cultures were extracted with Triton X-100, however, a subpopulation of cholesterol molecules remained colocalized with cytoskeleton in the membrane sheets. Activation of two well-characterized signaling pathways that differentially affect microtubule and actin filament stability in membrane sheets resulted in an apparent massive lateral movement of cholesterol molecules away from membrane regions overlying internal MBP domains to membrane tracts directly overlying cytoplasmic cytoskeletal veins. Depolymerization of microtubules by colchicine resulted in redistribution of cholesterol directly over actin filaments, whereas depolymerization of actin filaments by cytochalasin B resulted in redistribution of cholesterol directly over CNPase/microtubular veins. These data suggest that cholesterol forms an association with cytoskeletal components or proteins associated with cytoskeleton. These data also suggest that cholesterol, via interactions with cytoskeleton, plays a role in signaling pathways in oligodendrocyte membrane sheets.

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Identification of GTP‐ binding proteins in myelin and oligodendrocyte membranes

Cited by 45 publications

References 35 publications

GapIII, a new brain‐enriched member of the GTPase‐activating protein family

GapIII, a new brain‐enriched member of the GTPase‐activating protein family

Arachidonic acid inhibits myelin basic protein phosphorylation in cultured oligodendrocytes

Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways

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