RRC ID 46513
著者 Sun T, Wang X, Lu Q, Ren H, Zhang H.
タイトル CUP-5, the C. elegans ortholog of the mammalian lysosomal channel protein MLN1/TRPML1, is required for proteolytic degradation in autolysosomes.
ジャーナル Autophagy
Abstract The process of macroautophagy (herein referred to as autophagy) involves the formation of a closed double-membrane structure, called the autophagosome, and its subsequent fusion with lysosomes to form an autolysosome. Lysosomes are regenerated from autolysosomes after degradation of the sequestrated materials. In this study, we showed that mutations in cup-5, encoding the C. elegans Mucolipin 1 homolog, cause defects in the autophagy pathway. In cup-5 mutants, a variety of autophagy substrates accumulate in enlarged vacuoles that display characteristics of late endosomes and lysosomes, indicating defective proteolytic degradation in autolysosomes. We further revealed that lysosomes in coelomocytes (scavenger cells located in the body cavity) are smaller in size and more numerous in mutants with loss of autophagy activity. Furthermore, the enlarged vacuole accumulation abnormality and embryonic lethality of cup-5 mutants are partially suppressed by reduced autophagy activity. Our results indicate that the basal constitutive level of autophagy activity regulates the size and number of lysosomes and provides insights into the molecular mechanisms underlying mucolipidosis type IV disease.
巻・号 7(11)
ページ 1308-15
公開日 2011-11-1
DOI 10.4161/auto.7.11.17759
PII 17759
PMID 21997367
MeSH Alleles Animals Autophagy* Caenorhabditis elegans / cytology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Embryo, Nonmammalian / metabolism Embryo, Nonmammalian / pathology Humans Lysosomes / metabolism* Membrane Proteins / metabolism* Mutation / genetics Organelle Size Protein Structure, Quaternary Proteins / chemistry Proteolysis* Sequence Homology, Amino Acid* Substrate Specificity Transient Receptor Potential Channels / chemistry* Vacuoles / metabolism
IF 9.77
引用数 30
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm3425