Rate of Retrograde Transport of Cholera Toxin from the Plasma Membrane to the Golgi Apparatus and Endoplasmic Reticulum Decreases During Neuronal Development

Sofer, Anat; Futerman, Anthony H.

doi:10.1046/j.1471-4159.1996.67052134.x

Cited by 18 publications

(10 citation statements)

References 21 publications

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“…Endocytosis from selected regions of the plasma membrane would then result in the formation of endosomes in which the overall concentration of a given analogue did not match its concentration in the plasma membrane. It is interesting that a previous study using cholera toxin to monitor the internalization of GM1 ganglioside found that the rate of internalization of this marker was decreased significantly during maturation of hippocampal neurons (Sofer and Futerman, 1996). Although the current study used different methodology and cell types, our findings lead us to speculate that reduced internalization of certain cell‐surface lipids may be an important principle to consider in future studies of neuronal cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Internalization and Sorting of Plasma Membrane Sphingolipid Analogues in Differentiating Oligodendrocytes

Watanabe¹,

Asakura²,

Rodriguez³

et al. 1999

Journal of Neurochemistry

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Abstract:We studied the formation of early endosomes in differentiating oligodendrocytes and type-2 astrocytes, which are derived from common precursor cells in rat neonates, using fluorescent analogues of lactosylceramide (LacCer) and sulfatide labeled with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoic acid (BODIPY FL C 5 ). These sphingolipid analogues exhibit a concentration-dependent shift in their fluorescence emission maximum from green to red wavelengths that can be used to estimate the relative concentration of an analogue in the intracellular membranes of living cells by quantitative fluorescence microscopy. When oligodendrocytes at various stages of differentiation were incubated with 1 M BODIPY-sphingolipid at 10°C and washed, yellow/green plasma membrane fluorescence was observed. Quantitative studies confirmed that the amount of BODIPY-LacCer or -sulfatide incorporated into the plasma membrane of a given cell type was identical. When these cells were subsequently warmed to 37°C for 2-10 min to allow internalization to occur, the BODIPYsphingolipid analogues were distributed in a punctate pattern throughout the cytoplasm. Within individual cells labeled with BODIPY-sulfatide, some endosomes exhibited green fluorescence, whereas others emitted red/orange fluorescence. In contrast, when BODIPY-LacCer was used, only green endosomes were observed. Although this phenomenon could be observed at earlier stages of differentiation, it was most obvious in mature oligodendrocytes, where quantitative measurements of the red/green ratio of individual endosomes suggested about a threefold difference between the concentration of the LacCer and sulfatide analogues in endosomes. These results suggest that "lipid sorting" takes place during endocytosis in mature oligodendrocytes, resulting in selective exclusion of certain lipid species during the internalization process. This sorting event may result in the net addition of lipids to the differentiated oligodendrocyte plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Internalization and Sorting of Plasma Membrane Sphingolipid Analogues in Differentiating Oligodendrocytes

Watanabe¹,

Asakura²,

Rodriguez³

et al. 1999

Journal of Neurochemistry

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“…GM1 resides in caveolae (Parton, 1994). Cholera toxin is internalized from the plasma membrane primarily, but possibly not exclusively, via caveolae (Mukherjee et al, 1997;Shogomori and Futerman, 2001;Pelkmans and Helenius, 2002) and then reaches the Golgi system (Sofer and Futerman, 1996;Pelkmans and Helenius, 2002). Because GM1 also associates with Trk receptors, it has been speculated that cholera toxin may bind (and be trafficked) in a GM1-Trk-p75 complex .…”

Section: Cholera Toxinmentioning

confidence: 99%

“…Consistent with this notion, those internalized proteins that are most efficiently routed to an anterograde axonal pathway pass through the Golgi apparatus. These proteins include anterogradely transcytosed proteins such as lectins (WGA, Broadwell and Balin, 1985), cholera toxin (Sofer and Futerman, 1996;Shogomori and Futerman, 2001), tetanus toxin (Schwab and Thoenen, 1977a), as well as trophic factors . Internalized proteins that do not travel anterogradely or do so less efficiently, on the other hand, do not seem to be routed through the Golgi system (Claude et al, 1982;Butowt and von Bartheld, 2001).…”

Section: Pathways: Sortingmentioning

confidence: 99%

Axonal transport and neuronal transcytosis of trophic factors, tracers, and pathogens

Bartheld

2003

J. Neurobiol.

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Neurons can specifically internalize macromolecules, such as trophic factors, lectins, toxins, and other pathogens. Upon internalization in terminals, proteins can move retrogradely along axons, or, upon internalization at somatodendritic domains, they can move into an anterograde axonal transport pathway. Release of internalized proteins from neurons after either retrograde or anterograde axonal transport results in transcytosis and trafficking of proteins across multiple synapses. Recent studies of binding properties of several such proteins suggest that pathogens and lectins may utilize existing transport machineries designed for trafficking of trophic factors. Specific pathways may protect trophic factors, pathogens, and toxins from degradation after internalization and may target the trophic or pathogenic cargo for transcytosis after either retrograde or anterograde transport along axons. Elucidating the molecular mechanisms of sorting steps and transport pathways will further our understanding of trophic signaling and could be relevant for an understanding and possible treatment of neurological diseases such as rabies, Alzheimer's disease, and prion encephalopathies. At present, our knowledge is remarkably sparse about the types of receptors used by pathogens for trafficking, the signals that sort trophins or pathogens into recycling or degradation pathways, and the mechanisms that regulate their release from somatodendritic domains or axon terminals. This review intends to draw attention to potential convergences and parallels in trafficking of trophic and pathogenic proteins. It discusses axonal transport/trafficking mechanisms that may help to understand and eventually treat neurological diseases by targeted drug delivery.

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“…1987). From here, unlike molecules that are recycled back to the cell surface, or transported directly to lysosomes for degradation, CT is transported to the Golgi apparatus and then to the endoplasmic reticulum (Sofer and Futerman 1995, 1996). cAMP is generated (Orlandi et al .…”

mentioning

confidence: 99%

Cholesterol depletion by methyl‐β‐cyclodextrin blocks cholera toxin transport from endosomes to the Golgi apparatus in hippocampal neurons

Shogomori¹,

Futerman

2001

Journal of Neurochemistry

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We recently demonstrated that although cholera toxin (CT) is found in detergent-insoluble domains/rafts at the cell surface of cultured hippocampal neurons, it is internalized via a raftindependent mechanism. Thus, cholesterol depletion by methyl-b-cyclodextrin (MbCD) did not affect the rate of CT internalization from the plasma membrane, but did affect the rate of CT degradation, which occurs in lysosomes. In the current study, we analyze which step of CT intracellular transport is inhibited by MbCD. Whereas pre-incubation with MbCD completely blocked CT degradation, it had no effect on the degradation of wheat germ agglutinin (WGA) or bovine serum albumin (BSA), which are internalized by receptor-mediated and¯uid phase endocytosis, respectively. Brefeldin A also completely blocked CT degradation but had no effect on WGA or BSA degradation. In contrast, MbCD did not affect CT degradation, or CT-mediated cAMP generation, when added to neurons after CT had been transported to the Golgi apparatus. We conclude that CT transport from endosomes to the Golgi apparatus is cholesterol-dependent, whereas CT transport from the Golgi apparatus to lysosomes is cholesterol-independent.

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Rate of Retrograde Transport of Cholera Toxin from the Plasma Membrane to the Golgi Apparatus and Endoplasmic Reticulum Decreases During Neuronal Development

Cited by 18 publications

References 21 publications

Internalization and Sorting of Plasma Membrane Sphingolipid Analogues in Differentiating Oligodendrocytes

Internalization and Sorting of Plasma Membrane Sphingolipid Analogues in Differentiating Oligodendrocytes

Axonal transport and neuronal transcytosis of trophic factors, tracers, and pathogens

Cholesterol depletion by methyl‐β‐cyclodextrin blocks cholera toxin transport from endosomes to the Golgi apparatus in hippocampal neurons

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