Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking

Cellular Processes ◽

Endosomal Signaling ◽

Lipid Kinases ◽

Reported Data ◽

Phosphatidylinositol 3-kinases (PI3Ks) are critical regulators of many cellular processes including cell survival, proliferation, migration, cytoskeletal reorganization, and intracellular vesicular trafficking. They are a family of lipid kinases that phosphorylate membrane phosphoinositide lipids at the 3′ position of their inositol rings, and in mammals they are divided into three classes. The role of the class III PI3K Vps34 is well-established, but recent evidence suggests the physiological significance of class II PI3K isoforms in vesicular trafficking. This review focuses on the recently discovered functions of the distinct PI3K-C2α and PI3K-C2β class II PI3K isoforms in clathrin-mediated endocytosis and consequent endosomal signaling, and discusses recently reported data on class II PI3K isoforms in different physiological contexts in comparison with class I and III isoforms.

Essential Role of Class II Phosphatidylinositol-3-kinase-C2α in Sphingosine 1-Phosphate Receptor-1-mediated Signaling and Migration in Endothelial Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m112.409656 ◽

2012 ◽

Vol 288 (4) ◽

pp. 2325-2339 ◽

Cited By ~ 35

Author(s):

Kuntal Biswas ◽

Kazuaki Yoshioka ◽

Ken Asanuma ◽

Yasuo Okamoto ◽

Noriko Takuwa ◽

...

Keyword(s):

Endothelial Cells ◽

Essential Role ◽

Class Ii ◽

Sphingosine 1 Phosphate ◽

And Migration ◽

Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation

The Journal of Cell Biology ◽

10.1083/jcb.200107069 ◽

2001 ◽

Vol 155 (1) ◽

pp. 19-26 ◽

Cited By ~ 346

Author(s):

Otilia V. Vieira ◽

Roberto J. Botelho ◽

Lucia Rameh ◽

Saskia M. Brachmann ◽

Tsuyoshi Matsuo ◽

...

Keyword(s):

Functional Role ◽

Fluorescent Proteins ◽

Class I ◽

Class Iii ◽

Intracellular Parasites ◽

Selective Ablation ◽

Phagosomal Membrane ◽

Phagosomes acquire their microbicidal properties by fusion with lysosomes. Products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for phagosome formation, but their role in maturation is unknown. Using chimeric fluorescent proteins encoding tandem FYVE domains, we found that phosphatidylinositol 3-phosphate (PI[3]P) accumulates greatly but transiently on the phagosomal membrane. Unlike the 3′-phosphoinositides generated by class I PI 3-kinases which are evident in the nascent phagosomal cup, PI(3)P is only detectable after the phagosome has sealed. The class III PI 3-kinase VPS34 was found to be responsible for PI(3)P synthesis and essential for phagolysosome formation. In contrast, selective ablation of class I PI 3-kinase revealed that optimal phagocytosis, but not maturation, requires this type of enzyme. These results highlight the differential functional role of the two families of kinases, and raise the possibility that PI(3)P production by VPS34 may be targeted during the maturation arrest induced by some intracellular parasites.

Role of class III phosphatidylinositol 3-kinase during programmed nuclear death ofTetrahymena thermophila

Autophagy ◽

10.4161/auto.26929 ◽

2013 ◽

Vol 10 (2) ◽

pp. 209-225 ◽

Cited By ~ 11

Author(s):

Takahiko Akematsu ◽

Yasuhiro Fukuda ◽

Rizwan Attiq ◽

Ronald E Pearlman

Keyword(s):

Class Iii ◽

pH of endophagosomes controls association of their membranes with Vps34 and PtdIns(3)P levels

The Journal of Cell Biology ◽

10.1083/jcb.201702179 ◽

2017 ◽

Vol 217 (1) ◽

pp. 329-346 ◽

Cited By ~ 14

Author(s):

Amriya Naufer ◽

Victoria E.B. Hipolito ◽

Suriakarthiga Ganesan ◽

Akriti Prashar ◽

Vanina Zaremberg ◽

...

Keyword(s):

Filamentous Bacteria ◽

Class Iii ◽

Cellular Processes ◽

Ph Dependent ◽

Cellular Pathways ◽

Luminal Ph ◽

Phagocytic Cups ◽

Phagocytosis of filamentous bacteria occurs through tubular phagocytic cups (tPCs) and takes many minutes to engulf these filaments into phagosomes. Contravening the canonical phagocytic pathway, tPCs mature by fusing with endosomes. Using this model, we observed the sequential recruitment of early and late endolysosomal markers to the elongating tPCs. Surprisingly, the regulatory early endosomal lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) persists on tPCs as long as their luminal pH remains neutral. Interestingly, by manipulating cellular pH, we determined that PtdIns(3)P behaves similarly in canonical phagosomes as well as endosomes. We found that this is the product of a pH-based mechanism that induces the dissociation of the Vps34 class III phosphatidylinositol-3-kinase from these organelles as they acidify. The detachment of Vps34 stops the production of PtdIns(3)P, allowing for the turnover of this lipid by PIKfyve. Given that PtdIns(3)P-dependent signaling is important for multiple cellular pathways, this mechanism for pH-dependent regulation of Vps34 could be at the center of many PtdIns(3)P-dependent cellular processes.

Role of protein kinase A and class II phosphatidylinositol 3-kinase C2β in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2016.01.152 ◽

2016 ◽

Vol 470 (4) ◽

pp. 907-912 ◽

Cited By ~ 5

Author(s):

Ju Yeon Choi ◽

Seonghee Park

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Membrane Surface ◽

Surface Expression ◽

Class Ii ◽

Kinase A ◽

The class III phosphatidylinositol 3-kinase Vps34 in Saccharomyces cerevisiae

Biological Chemistry ◽

10.1515/hsz-2016-0288 ◽

2017 ◽

Vol 398 (5-6) ◽

pp. 677-685 ◽

Cited By ~ 6

Author(s):

Christina Reidick ◽

Fahd Boutouja ◽

Harald W. Platta

Keyword(s):

Saccharomyces Cerevisiae ◽

Functional Role ◽

Protein Sorting ◽

Endocytic Trafficking ◽

Class Iii ◽

Lipid Kinase ◽

Vacuolar Protein ◽

Abstract The class III phosphatidylinositol 3-kinase Vps34 (vacuolar protein sorting 34) catalyzes for the formation of the signaling lipid phosphatidylinositol-3-phopsphate, which is a central factor in the regulation of autophagy, endocytic trafficking and vesicular transport. In this article, we discuss the functional role of the lipid kinase Vps34 in Saccharomyces cerevisiae.