HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/C393    most recent 00019.2006v2 00019.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Ikonomov, O. C. Articles by Shisheva, A. Search for Related Content PubMed PubMed Citation Articles by Ikonomov, O. C. Articles by Shisheva, A.

CALL FOR PAPERS
Protein and Vesicle Trafficking, Cytoskeleton

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

Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan

Submitted 18 January 2006 ; accepted in final form 22 February 2006

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 PIKfyve^K1831E-positive vesicles co-localizing with dilated EEA1- and Rab5a^WT-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 PIKfyve^WT 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 PIKfyve^WT from early endosomes toward later compartments. Late endosomes/lysosomes marked by LAMP1 or Rab7 were dislocated from their typical perinuclear position upon PIKfyve^K1831E early expression. Cytosols derived from cells stably expressing PIKfyve^K1831E stimulated endosome fusion in vitro, whereas PIKfyve^WT-enriched cytosols had the opposite effect, consistent with PtdIns 3,5-P₂ production negatively regulating the endosome fusion. Together, our data indicate that PtdIns 3,5-P₂ defines specific endosome platforms at the onset of the degradation pathway to regulate the complex process of membrane remodeling and dynamics.

carrier vesicle; multivesicular bodies; PIKfyve; Rab5/EEA1/PtdINS3-P platforms; Rab7; LAMP1

This article has been cited by other articles:

				A. Shisheva Phosphoinositides in insulin action on GLUT4 dynamics: not just PtdIns(3,4,5)P3 Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E536 - E544. [Abstract] [Full Text] [PDF]

				C. Cao, J. M. Backer, J. Laporte, E. J. Bedrick, and A. Wandinger-Ness Sequential Actions of Myotubularin Lipid Phosphatases Regulate Endosomal PI(3)P and Growth Factor Receptor Trafficking Mol. Biol. Cell, August 1, 2008; 19(8): 3334 - 3346. [Abstract] [Full Text] [PDF]

				J. Kim, W. J. Jahng, D. Di Vizio, J. S. Lee, R. Jhaveri, M. A. Rubin, A. Shisheva, and M. R. Freeman The Phosphoinositide Kinase PIKfyve Mediates Epidermal Growth Factor Receptor Trafficking to the Nucleus Cancer Res., October 1, 2007; 67(19): 9229 - 9237. [Abstract] [Full Text] [PDF]