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 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.
Kypri
Elena
E
Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
Schmauch
Christian
C
Maniak
Markus
M
De Lozanne
Arturo
A
D000818:Animals; D002609:Chediak-Higashi Syndrome / Q000235:genetics; D003911:Dextrans / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism*; D008561:Membrane Fusion / Q000235:genetics / Q000502:physiology*; D018613:Microscopy, Confocal; D017494:Proton Pumps / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012235:Rhodamines; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
D003911:Dextrans; D005456:Fluorescent Dyes; C102161:LYST protein, human; D017494:Proton Pumps; D015800:Protozoan Proteins; D012235:Rhodamines; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; C009434:tetramethylrhodamine isothiocyanate; D016650:Fluorescein-5-isothiocyanate