Dynamic association of the PI3P-interacting Mon1-Ccz1 GEF with vacuoles is controlled through its phosphorylation by the type 1 casein kinase Yck3
| العنوان: | Dynamic association of the PI3P-interacting Mon1-Ccz1 GEF with vacuoles is controlled through its phosphorylation by the type 1 casein kinase Yck3 |
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| المؤلفون: | Christopher C. Brown, Christian Ungermann, Gus Lawrence, Rutilio A. Fratti, Surya Karunakaran, Blake A. Flood, Margarita Cabrera, Mirjana Nordmann |
| المصدر: | Molecular Biology of the Cell |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | animal structures, Saccharomyces cerevisiae Proteins, Phosphatidate Phosphatase, Vesicular Transport Proteins, Vacuole, Endosomes, Saccharomyces cerevisiae, Biology, environment and public health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Phosphatidylinositol Phosphates, Casein Kinase I, Organelle, Guanine Nucleotide Exchange Factors, Phosphatidylinositol, Phosphorylation, Molecular Biology, 030304 developmental biology, rab5 GTP-Binding Proteins, 0303 health sciences, rab7 GTP-Binding Proteins, Cell Biology, Articles, Class III Phosphatidylinositol 3-Kinases, Cell biology, enzymes and coenzymes (carbohydrates), Protein Transport, chemistry, Biochemistry, rab GTP-Binding Proteins, Membrane Trafficking, Vacuoles, Rab, Casein kinase 1, Guanine nucleotide exchange factor, 030217 neurology & neurosurgery, Protein Binding |
| الوصف: | Recruitment and activation of the late endosomal Rab Ypt7 require the GEF Mon1-Ccz1. Association of Mon1 with vacuoles depends on the lipid PI3P, and Mon1 is phosphorylated by the casein kinase Yck3. Phospho-Mon1 is subsequently released from vacuoles as part of a putative recycling mechanism. Maturation of organelles in the endolysosomal pathway requires exchange of the early endosomal GTPase Rab5/Vps21 for the late endosomal Rab7/Ypt7. The Rab exchange depends on the guanine nucleotide exchange factor activity of the Mon1-Ccz1 heterodimer for Ypt7. Here we investigate vacuole binding and recycling of Mon1-Ccz1. We find that Mon1-Ccz1 is absent on vacuoles lacking the phosphatidic acid phosphatase Pah1, which also lack Ypt7, the phosphatidylinositol 3-kinase Vps34, and the lipid phosphatidylinositol 3-phosphate (PI3P). Interaction of Mon1-Ccz1 with wild-type vacuoles requires PI3P, as shown in competition experiments. We also find that Mon1 is released from vacuoles during the fusion reaction and its release requires its phosphorylation by the type 1 casein kinase Yck3. In contrast, Mon1 is retained on vacuoles lacking Yck3 or when Mon1 phosphorylation sites are mutated. Phosphorylation and release of Mon1 is restored with addition of recombinant Yck3. Together the results show that Mon1 is recruited to endosomes and vacuoles by PI3P and, likely after activating Ypt7, is phosphorylated and released from vacuoles for recycling. |
| تدمد: | 1939-4586 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::783e09c4344343a3037906d5ac34cc8f https://pubmed.ncbi.nlm.nih.gov/24623720 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....783e09c4344343a3037906d5ac34cc8f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19394586 |
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