The BEACH Protein LvsB Is Localized on Lysosomes and Postlysosomes and Limits Their Fusion with Early Endosomes

The Chediak–Higashi syndrome (CHS) is a genetic disorder caused by the loss of the BEACH protein Lyst. Impaired lysosomal function in CHS patients results in many physiological problems, including immunodeficiency, albinism and neurological problems. Dictyostelium LvsB is the ortholog of mammalian L...

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Bibliographic Details
Published in:Traffic (Copenhagen, Denmark) Denmark), 2007-06, Vol.8 (6), p.774-783
Main Authors: Kypri, Elena, Schmauch, Christian, Maniak, Markus, Lozanne, Arturo De
Format: Article
Language:English
Subjects:
Animals
beige
Chediak-Higashi Syndrome - genetics
CHS
Dextrans - metabolism
Dictyostelium
Dictyostelium - cytology
Dictyostelium - genetics
Dictyostelium - metabolism
Endosomes - metabolism
Fluorescein-5-isothiocyanate
Fluorescent Dyes
Green Fluorescent Proteins - metabolism
Hydrogen-Ion Concentration
Lysosomes - metabolism
Lyst
Membrane Fusion - genetics
Membrane Fusion - physiology
Microscopy, Confocal
Proton Pumps - metabolism
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Rhodamines
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
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Summary:The Chediak–Higashi syndrome (CHS) is a genetic disorder caused by the loss of the BEACH protein Lyst. Impaired lysosomal function in CHS patients results in many physiological problems, including immunodeficiency, albinism and neurological problems. Dictyostelium LvsB is the ortholog of mammalian Lyst and is also important for lysosomal function. A knock‐in approach was used to tag LvsB with green fluorescent protein (GFP) and express it from its single chromosomal locus. GFP‐LvsB was observed on late lysosomes and postlysosomes. Loss of LvsB resulted in enlarged postlysosomes, in the abnormal localization of proton pumps on postlysosomes and their abnormal acidification. The abnormal postlysosomes in LvsB‐null cells were produced by the inappropriate fusion of early endosomal compartments with postlysosomal compartments. The intermixing of compartments resulted in a delayed transit of fluid‐phase marker through the endolysosomal system. These results support the model that LvsB and Lyst proteins act as negative regulators of fusion by limiting the heterotypic fusion of early endosomes with postlysosomal compartments.
ISSN:1398-9219
1600-0854
DOI:10.1111/j.1600-0854.2007.00567.x