The giant organelles in beige and Chediak-Higashi fibroblasts are derived from late endosomes and mature lysosomes.

Burkhardt, J.K.; Wiebel, F A; Hester, Susan; Argon, Yair

doi:10.1084/jem.178.6.1845

Cited by 124 publications

(100 citation statements)

References 43 publications

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“…Lyst is a large cytosolic protein containing WD domains at its C terminus (Barbosa et al, 1996). A genetic defect in both lyst and beige, a mouse homologue of lyst, leads to either enlargement and/or dysfunction of lysosome-related organelles, such as melanosomes, dense granules and cytolytic granules (Burkhardt et al, 1993;Shiflett et al, 2002;Ward et al, 2000). Several lines of evidence suggest that the lyst/beige protein is responsible for fission, rather than fusion.…”

Section: Discussionmentioning

confidence: 99%

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

Fujita

Yusuke

Imamura

et al. 2004

Journal of Cell Science

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IntroductionIn eukaryotic cells, there are two major routes to the lysosome/vacuole after exiting the trans-Golgi network (TGN) (Hunziker and Geuze, 1996;Kornfeld and Mellman, 1989). One is the biosynthetic pathway by which the cell delivers newly synthesized lysosomal enzymes and membrane proteins for the biogenesis and maintenance of lysosomes/vacuoles. The transport vesicles carrying the cargo molecules are budded from the TGN and mostly target endosomes prior to arriving at lysosomes/vacuoles. The other route is the so-called endocytic pathway by which the cell delivers various internalized ligands and the receptors from the plasma membrane (PM) to lysosomes/vacuoles for degradation. The ligand-receptor complexes, for instance the EGF/EGF-receptor, are segregated into the internal vesicles of endosomes (Futter et al., 1996). Subsets of receptors that recycle back to the PM, such as transferrin receptor and low-density lipoprotein receptor, are sequestered into clathrin-coated vesicles at recycling endosomes and are removed from the degradative pathways. In both pathways, endosomes play central roles in the sorting of cargo molecules and indeed, endosomes are meeting places for membrane traffic from both routes.By an extensive genetic analysis in the yeast Saccharomyces cerevisiae, more than 50 of the Vps (vacuolar protein sorting) genes involved in membrane transport to vacuoles were isolated (Raymond et al., 1992). The class E Vps family, one of the sub-groups of Vps mutants, exhibits a modest degree of secretion of newly synthesized carboxypeptidase Y (CPY), a soluble vacuolar enzyme, compared with other sub-classes of Vps mutants. In class E Vps mutants, both the 60 kDa V-2997 SKD1 belongs to the AAA-ATPase family and is one of the mammalian class E Vps (vacuolar protein sorting) proteins. Previously we have reported that the overexpression of an ATPase activity-deficient form of SKD1 (suppressor of potassium transport growth defect), SKD1(E235Q), leads the perturbation of membrane transport through endosomes and lysosomes, however, the molecular mechanism behind the action of SKD1 is poorly understood. We have identified two SKD1-binding proteins, SBP1 and mVps2, by yeast two-hybrid screening and we assign them as mammalian class E Vps proteins. The primary sequence of SBP1 indicates 22.5% identity with that of Vta1p from Saccharomyces cerevisiae, which was recently identified as a novel class E Vps protein binding to Vps4p. In fact, SBP1 binds directly to SKD1 through its C-terminal region (198-309). Endogenous SBP1 is exclusively localized to cytosol, however it is redirected to an aberrant endosomal structure, the E235Q compartment, in the cells expressing SKD1(E235Q). The ATPase activity of SKD1 regulates both the membrane association of, and assembly of, a large hetero-oligomer protein complex, containing SBP1, which is potentially involved in membrane transport through endosomes and lysosomes. The N-terminal half (1-157) of human SBP1 is identical to lyst-interacting protein 5 and intriguingly, SKD...

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Section: Discussionmentioning

confidence: 99%

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

Fujita

Yusuke

Imamura

et al. 2004

Journal of Cell Science

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“…Vesicular transport to and from the lysosome and late endosome is defective in patients with Chediak-Higashi syndrome, and in mutant beige mice (Barbosa et al 1996(Barbosa et al , 1997. In Chediak-Higashi syndrome, and in mutant beige mice, cells have giant, perinuclear vesicles with characteristics of late endosomes and lysosomes that arise from dysregulated homotypic fusion (Brandt et al 1975;Willingham et al 1981;Burkhardt et al 1993). Antisense expression of Rab9 produced cells that contained numerous large vacuoles, a phenotype resembling that of fibroblasts from patients with Chediak-Higashi syndrome (Davies et al 1997).…”

Section: Genomic Structure and Chromosome Mapping Of The Rab9-like Genementioning

confidence: 99%

cDNA cloning of a new member of the Ras superfamily, RAB9-like, on the human chromosome Xq22.1–q22.3 region

Seki¹,

Abe²,

Yoshikawa³

et al. 2000

J Hum Genet

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Members of the RAB protein family regulate vesicular trafficking and reside in specific intercellular compartments. A new member of the RAB family was identified through a public database search, and its fulllength cDNA was isolated from a human fetal brain cDNA library. The predicted protein product of the gene consists of 201 amino acid residues, and the protein has 86% similarity to human RAB9 at the amino acid level. We designated the new gene RAB9-like. Northern blot analysis showed that the gene was transcribed ubiquitously in various human tissues. A database search revealed that the gene is divided into three exons and spans approximately 7.2 kb of the genome DNA of chromosome Xq22.1-q22.3 region.

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“…In general, CHS is believed to be a lysosomal disease. It was concluded that giant granules in fibroblasts of beige mice are derived from mature lysosomes and from the late endocytic compartment [15]. Human neutrophils contain several granule subtypes (azurophil, specific, and gelatinase granules), in addition to the highly mobilizable secretory vesicles [for review see ref .…”

Section: Introductionmentioning

confidence: 99%

“…The origin of giant granules has been the subject of intense scrutiny in a variety of cells [1,4,[12][13][14][15]. In general, CHS is believed to be a lysosomal disease.…”

Section: Introductionmentioning

confidence: 99%

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

Kjeldsen

Calafat

Borregaard

1998

Journal of Leukocyte Biology

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The abnormal giant granules of ChediakHigashi syndrome (CHS) neutrophils in humans are thought to be derived from both azurophil and specific granules, whereas the presence of gelatinase granules and their contribution to giant granule formation has not been investigated previously. We have examined the ultrastructure and mobilization of neutrophil granules from a patient with CHS by immunogold electron microscopy and exocytosis experiments of isolated leukocytes. The giant granules contained the azurophil granule components myeloperoxidase and CD63. We found no evidence of involvement of specific or gelatinase granules in the formation of giant granules because lactoferrin and gelatinase were contained in normalappearing peroxidase-negative granules. On stimulation of leukocytes with N-formyl-methionyl-leucylphenylalanine and the calcium ionophore, ionomycin, there was a diminished exocytosis of myeloperoxidase in CHS compared with a healthy control, indicating a lack of mobilization of the giant granules. On the other hand, there was a normal or augmented release of lactoferrin and gelatinase in CHS neutrophils, with gelatinase granules being the most easily mobilized, as known from normal neutrophils. In conclusion, giant granules from CHS neutrophils originate from azurophil granules but not from the specific and gelatinase granules. J. Leukoc. Biol. 64: 72-77; 1998.

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The giant organelles in beige and Chediak-Higashi fibroblasts are derived from late endosomes and mature lysosomes.

Cited by 124 publications

References 43 publications

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

cDNA cloning of a new member of the Ras superfamily, RAB9-like, on the human chromosome Xq22.1–q22.3 region

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

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