Localized PtdIns 3,5-P2 synthesis to regulate early endosome dynamics and fusion

American Journal of Physiology. Cell Physiology
Ognian C IkonomovAssia Shisheva

Abstract

Perturbations in the intracellular PtdIns 3,5-P2 pool or the downstream transmission of PtdIns 3,5-P2 signals often result in a gradual development of gross morphological changes in the pleiomorphic multivesicular endosomes, culminating with the appearance of cytoplasmic vacuoles. To identify the onset of PtdIns 3,5-P2 functional requirements along the endocytic system, in this study we characterized the morphological changes associated with early expression of the dominant-negative kinase-deficient form (K1831E) of the PtdIns 3,5-P2-producing kinase PIKfyve, before the formation of cytoplasmic vacuoles in transfected COS cells. Enlarged PIKfyveK1831E-positive vesicles co-localizing with dilated EEA1- and Rab5aWT-positive perinuclear endosomes were observed (WT, wild type). This was dependent on the presence of active forms of Rab5 and the generation of PtdIns 3-P-enriched platforms on early endosomess. Because PIKfyveWT did not substantially colocalize with EEA1- or Rab5-positive endosomes in COS cells, the dynamic PIKfyve-catalyzed PtdIns 3-to-PtdIns 3,5-P2 switch was suggested to drive away PIKfyveWT from early endosomes toward later compartments. Late endosomes/lysosomes marked by LAMP1 or Rab7 were dislocated from their ty...Continue Reading

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Citations

Dec 31, 2009·The Journal of Membrane Biology·Mentor SopjaniFlorian Lang
Dec 6, 2008·The Journal of Biological Chemistry·Ognian C IkonomovAssia Shisheva
Oct 2, 2009·Human Molecular Genetics·Cole J FergusonMiriam H Meisler
Sep 18, 2010·Science·Miwa SasaiAkiko Iwasaki
May 22, 2008·American Journal of Physiology. Endocrinology and Metabolism·Assia Shisheva
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