Phosphatidylinositol 5-kinase Stimulates Apical Biosynthetic Delivery Via an Arp2/3-dependent Mechanism.
From: Laboratory of Epithelial Cell Biology, Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
The Journal of biological chemistry
- Publish Date: Jun 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 22
- Pages: 15376-84
- Medium: Print
- Language: English
- Citation (JAMA): Guerriero Christopher J, Weixel Kelly M, Bruns Jennifer R, et al. Phosphatidylinositol 5-kinase Stimulates Apical Biosynthetic Delivery Via an Arp2/3-dependent Mechanism.. J. Biol. Chem. Jun 2006;281:15376-84
Abstract
The mechanisms by which polarized epithelial cells target distinct carriers enriched in newly synthesized proteins to the apical or basolateral membrane remain largely unknown. Here we investigated the effect of phosphatidylinositol metabolism and modulation of the actin cytoskeleton, two regulatory mechanisms that have individually been suggested to function in biosynthetic traffic, on polarized traffic in Madin-Darby canine kidney cells. Overexpression of phosphatidylinositol 5-kinase (PI5K) increased actin comet frequency in Madin-Darby canine kidney cells and concomitantly stimulated trans-Golgi network (TGN) to apical membrane delivery of the raft-associated protein influenza hemagglutinin (HA), but did not affect delivery of a non-raft-associated apical protein or a basolateral marker. Modulation of actin comet formation by pharmacologic means, by overexpression of the TGN-localized inositol polyphosphate 5-phosphatase Ocrl, or by blockade of Arp2/3 function had parallel effects on the rate of apical delivery of HA. Moreover, HA released from a TGN block was colocalized in transport carriers in association with PI5K and actin comets. Inhibition of Arp2/3 function in combination with microtubule depolymerization led to a virtual block in HA delivery, suggesting synergistic coordination of these cytoskeletal assemblies in membrane transport. Our results suggest a previously unidentified role for actin comet-mediated propulsion in the biosynthetic delivery of a subset of apical proteins.
Mesh Headings (Keywords): Actin-Related Protein 2-3 Complex, Animals, Biological Transport, Active, Cell Line, Cell Polarity, Dogs, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Kinetics, Membrane Microdomains, Mice, Phosphotransferases (Alcohol Group Acceptor), Recombinant Proteins, trans-Golgi Network
Check for Full Text / PubMed Unique Identifier (PMID): 16601114
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