The Effect of Lysosomotropic Amines onBeigeMouse Cells

Davis, Steven G.; Lyerla, Timothy A.

doi:10.1006/excr.1997.3767

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…LGP85-induced large vacuoles are acidic Lysosomotropic amines, such as NH4Cl and methylamine, have been shown to cause vacuolation of acidic compartments (Ohkuma and Poole, 1981;Davis and Lyerla, 1997). The effect of these amines is due to raising the pH of intra-endosomal/lysosomal compartments by accumulation of protonated base (Ohkuma and Poole, 1981).…”

Section: Cholesterol Accumulates In Large Swollen Vacuoles Induced Bymentioning

confidence: 99%

A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology

Kuronita

Eskelinen

Fujita

et al. 2002

Journal of Cell Science

143

109

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LGP85 (LIMP II) is a type III transmembrane glycoprotein that is located primarily in the limiting membranes of lysosomes and late endosomes. Despite being the abundant molecule of these compartments, whether LGP85 merely resides as one of the constituents of these membranes or plays a role in the regulation of endosome and lysosome biogenesis remains unclear. To elucidate these questions, we examined the effects of overexpression of LGP85 on the morphology and membrane traffic of the endosomal/lysosomal system. Here we demonstrate that overexpression of LGP85 causes an enlargement of early endosomes and late endosomes/lysosomes. Such a morphological alteration was not observed by overexpression of other lysosomal membrane proteins, LGP107(LAMP-1) or LGP96 (LAMP-2), reflecting a LGP85-specific function. We further demonstrate that overexpression of LGP85 impairs the endocytic membrane traffic out of these enlarged compartments, which may be correlated with or account for the accumulation of cholesterol observed in these compartments. Interestingly, co-transfection of LGP85 and the dominant-negative form of Rab5b (Rab5bS34N) abolished the formation of large vacuoles, suggesting that the GTP-bound active form of Rab5b is involved in the enlargement of endosomal/lysosomal compartments induced by overexpression of LGP85. Thus,these findings provide important new insights into the role of LGP85 in the biogenesis and the maintenance of endosomes/lysosomes. We conclude that LGP85 may participate in reorganizing the endosomal/lysosomal compartments.

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Section: Cholesterol Accumulates In Large Swollen Vacuoles Induced Bymentioning

confidence: 99%

A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology

Kuronita

Eskelinen

Fujita

et al. 2002

Journal of Cell Science

143

109

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“…Beige mice are characterized by having enlarged lysosomes in their NK cells due to increased fluidity of cellular membranes and organelle fusion (Davis and Lyerla, 1997). NK cells from beige mice are incapable of in vitro natural cytolytic activity against tumor cells that are ordinarily NK sensitive (Talmadge et al, 1980).…”

mentioning

confidence: 99%

The Modulation of B16BL6 Melanoma Metastasis Is Not Directly Mediated by Cytolytic Activity of Natural Killer Cells in Alcohol‐Consuming Mice

Spitzer

Núñez

Meadows

et al. 2000

Alcoholism Clin & Exp Res

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“…These agents are membranepermeable weak bases and can form vacuoles in the cytoplasm (Ohkuma and Poole 1981) as well as other weak bases such as trimethylamine, triethanolamine, and ammonium chloride (NH 4 Cl) (Yang et al 1965;Seglen and Reith 1976;Ohkuma and Poole 1981;Cover et al 1993;Davis and Lyerla 1997;Ohkuma and Takano 1997). The membrane-permeable weak bases in the extracellular milieu can enter the cytoplasm, and then accumulate in the membranous acidic organelles such as lysosomes after protonation inside the organelles (Ohkuma and Poole 1981;Wada et al 1992;Arai et al 2002).…”

Section: Introductionmentioning

confidence: 97%

Effects of 4-Aminopyridine on Organelle Movement in Cultured Mouse Dorsal Root Ganglion Neurites

Hiruma

Kawakami

2009

J Mol Neurosci

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Aminopyridines, widely used as a K(+) channel blocker, are membrane-permeable weak bases and have the ability to form vacuoles in the cytoplasm. The vacuoles originate from acidic organelles such as lysosomes. Here, we investigated the effects of 4-aminopyridine (4-AP) on organelle movement in neurites of cultured mouse dorsal root ganglion (DRG) neurons by using video-enhanced microscopy. Some experiments were carried out using fluorescent dyes for lysosomes and mitochondria and confocal microscopy. Treatment of DRG neurons with 4 mM 4-AP caused Brownian movement of some lysosomes within 5 min. The Brownian movement gradually became rapid and vacuoles were formed around individual lysosomes 10-20 min after the start of treatment. Axonal transport of organelles was inhibited by 4-AP. Lysosomes showing Brownian movement were not transported in longitudinal direction of the neurite and the transport of mitochondria was interrupted by vacuoles. The 4-AP-induced Brownian movement of lysosomes with vacuole formation and inhibition of axonal transport were prevented by the simultaneous treatment with vacuolar H(+) ATPase inhibitor bafilomycin A1 or in Cl(-)-free SO(4)(2-) medium. These results indicate that changes in organelle movement by 4-AP are related to vacuole formation and the vacuolar H(+) ATPase and Cl(-) are required for the effects of 4-AP.

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The Effect of Lysosomotropic Amines onBeigeMouse Cells

Cited by 6 publications

References 16 publications

A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology

A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology

The Modulation of B16BL6 Melanoma Metastasis Is Not Directly Mediated by Cytolytic Activity of Natural Killer Cells in Alcohol‐Consuming Mice

Effects of 4-Aminopyridine on Organelle Movement in Cultured Mouse Dorsal Root Ganglion Neurites

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