Phosphatidylinositol 4-Kinaseβ Is Critical for Functional Association of rab11 with the Golgi Complex

Graaf, Petra de; Zwart, Wilbert; Dijken, Remco A.J. van; Deneka, Magdalena; Schulz, Thomas; Geijsen, Niels; Coffer, Paul J.; Gadella, Bart M.; Verkleij, Arie J.; Sluijs, Peter van der; Henegouwen, Paul M.P. van Bergen en

doi:10.1091/mbc.e03-12-0862

Cited by 134 publications

(114 citation statements)

References 38 publications

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“…PIK4CB/PI4KIII␤ appears in a distinct cluster with Rab1C/Rab35 and YIP3/PRA1, hence predicting a potential role for PIK4CB/PI4KIII␤ in ER-to-Golgi and Golgi transport regulated by the Rab1C/ Rab35 hub. We also noted that PIK4CB/PI4KIII␤ clusters with Rab11A associated with the apical recycling endosomes (Wang et al, 2000), confirming a recent finding that the former is requisite for the functional association of the latter with the Golgi complex (de Graaf et al, 2004). Cellular PI(3) kinase activities need to be balanced by counteracting PI(3) phosphatase activities.…”

Section: Rab Effectorssupporting

confidence: 87%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

115

107

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Rab GTPases and SNARE fusion proteins direct cargo trafficking through the exocytic and endocytic pathways of eukaryotic cells. We have used steady state mRNA expression profiling and computational hierarchical clustering methods to generate a global overview of the distribution of Rabs, SNAREs, and coat machinery components, as well as their respective adaptors, effectors, and regulators in 79 human and 61 mouse nonredundant tissues. We now show that this systems biology approach can be used to define building blocks for membrane trafficking based on Rab-centric protein activity hubs. These Rab-regulated hubs provide a framework for an integrated coding system, the membrome network, which regulates the dynamics of the specialized membrane architecture of differentiated cells. The distribution of Rab-regulated hubs illustrates a number of facets that guides the overall organization of subcellular compartments of cells and tissues through the activity of dynamic protein interaction networks. An interactive website for exploring datasets comprising components of the Rab-regulated hubs that define the membrome of different cell and organ systems in both human and mouse is available at http://www.membrome.org/. INTRODUCTIONUnderstanding the molecular basis for the organization of the exocytic and endocytic membrane trafficking pathways in the eukaryotic cell remains a formidable challenge. The foundation of these pathways is the lipid bilayer that separates different subcellular compartments, their distinguishing features encoded by phospholipid composition, and unique sets of integral and peripheral membrane proteins. By harnessing and regulating the fundamental processes of membrane fission and fusion through the action of protein complexes, the lipid bilayer can be exploited to produce a variety of distinct subcellular compartments with unique chemical environments that play essential roles in cell and organ function. Moreover, it is now evident that these subcellular compartments are dynamic structures in continuous and specific communication through carrier vesicles and tubules that mobilize cargo to specific destinations. They can be disassembled and reassembled in a remarkably facile manner in response to cell signaling pathways, mitosis, or by simple chemical perturbants.Implicit in these dynamic pathways is the need to systematically and reversibly regulate protein interactions. Although traditional phylogenetic analyses provided significant insights into the diversity of components that direct membrane traffic (Pereira-Leal and Seabra, 2000;Chen and Scheller, 2001;Pereira-Leal and Seabra, 2001), our understanding of the basic cellular building blocks that organize this diversity into contiguous pathways is still fragmentary. Reductionist approaches using biochemical and molecular tools also provide important insights into specific steps of a pathway. However, understanding the global interconnectivities of complex biological pathways, such as cargo trafficking, will require new approaches utilizing modern ...

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Section: Rab Effectorssupporting

confidence: 87%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

115

107

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“…To establish which Golgi compartment contained ORP9L, coimmunofluorescence experiments were conducted with cis (giantin), cis/ medial (PI-4 kinase III␤), and trans-Golgi/TGN (␥-adaptin) markers (de Graaf et al, 2004;Weixel et al, 2005; Figure 3). Immunofluorescence was performed in control cells and cells treated with nocodazole to fragment the Golgi into mini-stacks to enhance visualization.…”

Section: Ph and Sterol-binding Domains Control Orp9lmentioning

confidence: 99%

Oxysterol Binding Protein–related Protein 9 (ORP9) Is a Cholesterol Transfer Protein That Regulates Golgi Structure and Function

Ngo

Ridgway

2009

MBoC

161

201

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Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large gene family that differentially localize to organellar membranes, reflecting a functional role in sterol signaling and/or transport. OSBP partitions between the endoplasmic reticulum (ER) and Golgi apparatus where it imparts sterol-dependent regulation of ceramide transport and sphingomyelin synthesis. ORP9L also is localized to the ER-Golgi, but its role in secretion and lipid transport is unknown. Here we demonstrate that ORP9L partitioning between the trans-Golgi/trans-Golgi network (TGN), and the ER is mediated by a phosphatidylinositol 4-phosphate (PI-4P)-specific PH domain and VAMP-associated protein (VAP), respectively. In vitro, both OSBP and ORP9L mediated PI-4P-dependent cholesterol transport between liposomes, suggesting their primary in vivo function is sterol transfer between the Golgi and ER. Depletion of ORP9L by RNAi caused Golgi fragmentation, inhibition of vesicular somatitus virus glycoprotein transport from the ER and accumulation of cholesterol in endosomes/lysosomes. Complete cessation of protein transport and cell growth inhibition was achieved by inducible overexpression of ORP9S, a dominant negative variant lacking the PH domain. We conclude that ORP9 maintains the integrity of the early secretory pathway by mediating transport of sterols between the ER and trans-Golgi/TGN. INTRODUCTIONThe Golgi apparatus is a highly compartmentalized organelle that serves as a nexus for the processing, sorting, and vesicular transport of protein and lipid cargo between organelles. Regulation of vesicular transport is dependent on coat proteins and factors that control coat assembly/disassembly, as well as membrane dynamics and individual lipid regulators. A continuing challenge is the identification of the proteins responsible for spatial generation of Golgi lipid regulators by localized synthesis and/or transport (Huijbregts et al., 2000;De Matteis et al., 2007). In this study we investigated one such lipid-binding protein, oxysterol-binding protein (OSBP)-related protein 9 (ORP9), and its role in endoplasmic reticulum (ER)-to-Golgi transport.Lipid synthesis and transport to the Golgi apparatus regulates local and distal cellular functions. For example, synthesis of sphingomyelin (SM) and glycosphingolipids (Huitema et al., 2004) in combination with cholesterol is required for raft assembly in the Golgi and cargo delivery to the apical surface of polarized cells (Hoekstra et al., 2003). SM synthesis in the Golgi apparatus is dependent on delivery of ceramide from the ER by the ceramide transfer protein (CERT; Hanada et al., 2003). Ceramide transport by CERT involves binding of a phosphatidylinositol 4-phosphate (PI-4P)-specific pleckstrin homology (PH) domain to the Golgi apparatus and interaction with vesicle-associated membrane protein (VAMP)-associated-protein (VAP) by the "two phenylalanines in an acidic tract" (FFAT) motif (Hanada et al., 2003). In addition, CERT activates protein kinase D activity and secretory t...

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“…Surprisingly, PI4KIIIb-mediated Akt activation is not dependent on PI4KIIIb lipid kinase activity, its interaction with the small GTPase, Rab11a seems to be critical. Rab11aa regulates slow endosomal recycling, and has previously been shown to interact with PI4KIIIb (31,32). Our work suggests that PI4KIIIb has an important role in breast cancer and that cooperation between Rab11a and PI4KIIIb represents a novel Akt activation pathway.…”

Section: Introductionmentioning

confidence: 52%

“…The endosomal trafficking protein Rab11a was an attractive candidate as it had already been shown to bind to PI4KIIIb independently of its kinase function (32,45). We first verified that PI4KIIIb and Rab11a interact in our cells lines by coimmunoprecipitation.…”

Section: Pi4kiiib Activates Akt Via Pi(345)p 3 Signalingmentioning

confidence: 62%

“…KD-PI4KIIIb contains a substitution of an aspartic acid residue for alanine at position 656, rendering it catalytically inactive (44). Previous work has demonstrated that the PI4K activity of KD-PI4KIIIb is <0.2% that of WT-PI4KIIIb (32,44). Two independently derived cell lines expressing KD-PI4KIIIb showed significant increases ($2-fold) in Akt phosphorylation at Thr308 and at Ser473 as compared with the vector control and at levels comparable with those observed in BT549 cells ectopically expressing WT-PI4KIIIb (Fig.…”

Section: Pi4kiiib Activates Akt Via Pi(345)p 3 Signalingmentioning

confidence: 99%

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