Recycling is a limiting step for receptor-mediated endocytosis. We first report three in vitro or in vivo evidences that class III PI3K/VPS34 is the key PI3K isoform regulating apical recycling. A substractive approach, comparing in OK cells a pan-class I/II/III PI3K inhibitor (LY294002) with a class I/II PI3K inhibitor (ZSTK474), suggested that class III PI3K/VPS34 inhibition induced selective apical endosome swelling and sequestration of the endocytic receptor, megalin/LRP-2, causing surface down-regulation. GFP-(FYVE)x2 overexpression to sequester PI(3)P caused undistinguishable apical endosome swelling. In mouse kidney proximal tubular cells, conditional Vps34 inactivation also led to vacuolation and intracellular megalin redistribution. We next report that removal of LY294002 from LY294002-treated OK cells induced a spectacular burst of recycling tubules and restoration of megalin surface pool. Acute triggering of recycling tubules revealed recruitment of dynamin-GFP and dependence of dynamin-GTPase, guidance directionality by microtubules, and suggested that a microfilamentous net constrained endosomal swelling. We conclude that (i) besides its role in endosome fusion, PI3K-III is essential for endosome fission/recycling; and (ii) besides its role in endocytic entry, dynamin also supports tubulation of recycling endosomes. The unleashing of recycling upon acute reversal of PI3K inhibition may help study its dynamics and associated machineries.
Rodriguez-Boulan Enrique, Kreitzer Geri, Müsch Anne, Organization of vesicular trafficking in epithelia, 10.1038/nrm1593
Christ Annabel, Christa Anna, Kur Esther, Lioubinski Oleg, Bachmann Sebastian, Willnow Thomas E., Hammes Annette, LRP2 Is an Auxiliary SHH Receptor Required to Condition the Forebrain Ventral Midline for Inductive Signals, 10.1016/j.devcel.2011.11.023
Gajera C. R., Emich H., Lioubinski O., Christ A., Beckervordersandforth-Bonk R., Yoshikawa K., Bachmann S., Christensen E. I., Gotz M., Kempermann G., Peterson A. S., Willnow T. E., Hammes A., LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic niche, 10.1242/jcs.065912
Nykjaer Anders, Dragun Duska, Walther Diego, Vorum Henrik, Jacobsen Christian, Herz Joachim, Melsen Flemming, Christensen Erik Ilsoe, Willnow Thomas E, An Endocytic Pathway Essential for Renal Uptake and Activation of the Steroid 25-(OH) Vitamin D3, 10.1016/s0092-8674(00)80655-8
Fyfe J. C., The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless, 10.1182/blood-2003-08-2852
Tanos B, Rodriguez-Boulan E, The epithelial polarity program: machineries involved and their hijacking by cancer, 10.1038/onc.2008.345
De Matteis Maria Antonietta, Luini Alberto, Mendelian Disorders of Membrane Trafficking, 10.1056/nejmra0910494
Christensen Erik Ilsø, Birn Henrik, Megalin and cubilin: multifunctional endocytic receptors, 10.1038/nrm778
Verroust Pierre J., Birn Henrik, Nielsen Rikke, Kozyraki Renata, Christensen Erik I., The tandem endocytic receptors megalin and cubilin are important proteins in renal pathology, 10.1046/j.1523-1755.2002.00501.x
Christensen, Eur J Cell Biol, 29, 43 (1982)
Kerjaschki D., Farquhar M. G., The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border., 10.1073/pnas.79.18.5557
Nykjaer Anders, Willnow Thomas E., The low-density lipoprotein receptor gene family: a cellular Swiss army knife?, 10.1016/s0962-8924(02)02282-1
Nielsen R., Courtoy P. J., Jacobsen C., Dom G., Lima W. R., Jadot M., Willnow T. E., Devuyst O., Christensen E. I., Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells, 10.1073/pnas.0700330104
Anzenberger U., Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros, 10.1242/jcs.02954
Christ Annabel, Terryn Sara, Schmidt Vanessa, Christensen Erik I., Huska Matthew R., Andrade-Navarro Miguel A., Hübner Norbert, Devuyst Olivier, Hammes Annette, Willnow Thomas E., The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo, 10.1038/ki.2010.169
Verroust P. J., Megalin and cubilin--the story of two multipurpose receptors unfolds, 10.1093/ndt/17.11.1867
Zerial Marino, Christoforidis Savvas, McBride Heidi M., Burgoyne Robert D., 10.1038/17618
Sönnichsen Birte, De Renzis Stefano, Nielsen Erik, Rietdorf Jens, Zerial Marino, Distinct Membrane Domains on Endosomes in the Recycling Pathway Visualized by Multicolor Imaging of Rab4, Rab5, and Rab11, 10.1083/jcb.149.4.901
van Dam Ellen M., ten Broeke Toine, Jansen Karen, Spijkers Patricia, Stoorvogel Willem, Endocytosed Transferrin Receptors Recycle via Distinct Dynamin and Phosphatidylinositol 3-Kinase-dependent Pathways, 10.1074/jbc.m206271200
Roux Aurélien, Uyhazi Katherine, Frost Adam, De Camilli Pietro, GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission, 10.1038/nature04718
Mesaki Kumi, Tanabe Kenji, Obayashi Masanori, Oe Natsuko, Takei Kohji, Fission of Tubular Endosomes Triggers Endosomal Acidification and Movement, 10.1371/journal.pone.0019764
Lowe, AMA Am J Dis Child, 83, 164 (1952)
Choudhury R., Lowe Syndrome Protein OCRL1 Interacts with Clathrin and Regulates Protein Trafficking between Endosomes and the Trans-Golgi Network, 10.1091/mbc.e05-02-0120
Vicinanza Mariella, Di Campli Antonella, Polishchuk Elena, Santoro Michele, Di Tullio Giuseppe, Godi Anna, Levtchenko Elena, De Leo Maria Giovanna, Polishchuk Roman, Sandoval Lisette, Marzolo Maria-Paz, De Matteis Maria Antonietta, OCRL controls trafficking through early endosomes via PtdIns4,5P2-dependent regulation of endosomal actin : OCRL controls endocytic receptor recycling, 10.1038/emboj.2011.354
Traer Colin J., Rutherford Anna C., Palmer Krysten J., Wassmer Thomas, Oakley Jacqueline, Attar Naomi, Carlton Jez G., Kremerskothen Joachim, Stephens David J., Cullen Peter J., SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment, 10.1038/ncb1656
Cullen Peter J., Endosomal sorting and signalling: an emerging role for sorting nexins, 10.1038/nrm2427
Shinozaki-Narikawa Naeko, Kodama Tatsuhiko, Shibasaki Yoshikazu, Cooperation of Phosphoinositides and BAR Domain Proteins in Endosomal Tubulation, 10.1111/j.1600-0854.2006.00480.x
Gottlieb T. A., Actin microfilaments play a critical role in endocytosis at the apical but not the basolateral surface of polarized epithelial cells, 10.1083/jcb.120.3.695
Eker, J Biol Chem, 269, 18607 (1994)
Apodaca Gerard, Endocytic Traffic in Polarized Epithelial Cells: Role of the Actin and Microtubule Cytoskeleton : Role of Cytoskeleton in Endocytic Traffic, 10.1034/j.1600-0854.2001.020301.x
Maples Christopher J., Ruiz Wily G., Apodaca Gerard, Both Microtubules and Actin Filaments Are Required for Efficient Postendocytotic Traffic of the Polymeric Immunoglobulin Receptor in Polarized Madin-Darby Canine Kidney Cells, 10.1074/jbc.272.10.6741
Sheff D. R., Actin Dependence of Polarized Receptor Recycling in Madin-Darby Canine Kidney Cell Endosomes, 10.1091/mbc.01-07-0320
MERRIFIELD C, Neural Wiskott Aldrich Syndrome Protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts, 10.1078/0171-9335-00356
Derivery Emmanuel, Sousa Carla, Gautier Jérémie J., Lombard Bérangère, Loew Damarys, Gautreau Alexis, The Arp2/3 Activator WASH Controls the Fission of Endosomes through a Large Multiprotein Complex, 10.1016/j.devcel.2009.09.010
Puthenveedu Manojkumar A., Lauffer Benjamin, Temkin Paul, Vistein Rachel, Carlton Peter, Thorn Kurt, Taunton Jack, Weiner Orion D., Parton Robert G., von Zastrow Mark, Sequence-Dependent Sorting of Recycling Proteins by Actin-Stabilized Endosomal Microdomains, 10.1016/j.cell.2010.10.003
Lima W. R., Parreira K. S., Devuyst O., Caplanusi A., N'Kuli F., Marien B., Van Der Smissen P., Alves P. M.S., Verroust P., Christensen E. I., Terzi F., Matter K., Balda M. S., Pierreux C. E., Courtoy P. J., ZONAB Promotes Proliferation and Represses Differentiation of Proximal Tubule Epithelial Cells, 10.1681/asn.2009070698
Brunskill N J, Stuart J, Tobin A B, Walls J, Nahorski S, Receptor-mediated endocytosis of albumin by kidney proximal tubule cells is regulated by phosphatidylinositide 3-kinase., 10.1172/jci1923
Cupers P., Clathrin polymerization is not required for bulk-phase endocytosis in rat fetal fibroblasts, 10.1083/jcb.127.3.725
Tyteca D, Azithromycin, a Lysosomotropic Antibiotic, Has Distinct Effects on Fluid-Phase and Receptor-Mediated Endocytosis, but Does Not Impair Phagocytosis in J774 Macrophages, 10.1006/excr.2002.5613
Mayor Satyajit, Pagano Richard E., Pathways of clathrin-independent endocytosis, 10.1038/nrm2216
Christensen E. I., Devuyst O., Dom G., Nielsen R., Van Der Smissen P., Verroust P., Leruth M., Guggino W. B., Courtoy P. J., Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules, 10.1073/pnas.1432873100
Erdmann Kai S., Mao Yuxin, McCrea Heather J., Zoncu Roberto, Lee Sangyoon, Paradise Summer, Modregger Jan, Biemesderfer Daniel, Toomre Derek, De Camilli Pietro, A Role of the Lowe Syndrome Protein OCRL in Early Steps of the Endocytic Pathway, 10.1016/j.devcel.2007.08.004
Kong De-xin, Yamori Takao, ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system, 10.1038/aps.2010.150
Alessi, EMBO J, 15, 6541 (1996)
Schreiner Ryan, Frindt Gustavo, Diaz Fernando, Carvajal-Gonzalez Jose M., Perez Bay Andrés E., Palmer Lawrence G., Marshansky Vladimir, Brown Dennis, Philp Nancy J., Rodriguez-Boulan Enrique, The absence of a clathrin adapter confers unique polarity essential to proximal tubule function, 10.1038/ki.2010.166
Byfield Maya P., Murray James T., Backer Jonathan M., hVps34 Is a Nutrient-regulated Lipid Kinase Required for Activation of p70 S6 Kinase, 10.1074/jbc.m507201200
Kosaka Toshio, Ikeda Kazuo, Possible temperature-dependent blockage of synaptic vesicle recycling induced by a single gene mutation indrosophila, 10.1002/neu.480140305
Takei Kohji, McPherson Peter S., Schmid Sandra L., Camilli Pietro De, Tubular membrane invaginations coated by dynamin rings are induced by GTP-γS in nerve terminals, 10.1038/374186a0
Maurer M. E., Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein, 10.1242/jcs.02650
Nagai J., Mutually dependent localization of megalin and Dab2 in the renal proximal tubule, 10.1152/ajprenal.00292.2004
Bock Hans H., Jossin Yves, Liu Pingsheng, Förster Eckart, May Petra, Goffinet André M., Herz Joachim, Phosphatidylinositol 3-Kinase Interacts with the Adaptor Protein Dab1 in Response to Reelin Signaling and Is Required for Normal Cortical Lamination, 10.1074/jbc.m306416200
Chen J., Chen M. X., Fogo A. B., Harris R. C., Chen J.-K., mVps34 Deletion in Podocytes Causes Glomerulosclerosis by Disrupting Intracellular Vesicle Trafficking, 10.1681/asn.2012010101
Bechtel W., Helmstadter M., Balica J., Hartleben B., Kiefer B., Hrnjic F., Schell C., Kretz O., Liu S., Geist F., Kerjaschki D., Walz G., Huber T. B., Vps34 Deficiency Reveals the Importance of Endocytosis for Podocyte Homeostasis, 10.1681/asn.2012070700
Spiro D. J., Boll W., Kirchhausen T., Wessling-Resnick M., Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro., 10.1091/mbc.7.3.355
Kundra Robin, Kornfeld Stuart, Wortmannin Retards the Movement of the Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor and Its Ligand out of Endosomes, 10.1074/jbc.273.7.3848
Futter C.E., Collinson L.M., Backer J.M., Hopkins C.R., Human VPS34 is required for internal vesicle formation within multivesicular endosomes, 10.1083/jcb.200108152
Lenz Martin, Morlot Sandrine, Roux Aurélien, Mechanical requirements for membrane fission: Common facts from various examples, 10.1016/j.febslet.2009.11.012
Skjeldal F. M., Strunze S., Bergeland T., Walseng E., Gregers T. F., Bakke O., The fusion of early endosomes induces molecular-motor-driven tubule formation and fission, 10.1242/jcs.092569
Piwon Nils, Günther Willy, Schwake Michael, Bösl Michael R., Jentsch Thomas J., ClC-5 Cl--channel disruption impairs endocytosis in a
mouse model for Dent's disease, 10.1038/35042597
Reed A. A. C., Loh N. Y., Terryn S., Lippiat J. D., Partridge C., Galvanovskis J., Williams S. E., Jouret F., Wu F. T. F., Courtoy P. J., Nesbit M. A., Rorsman P., Devuyst O., Ashcroft F. M., Thakker R. V., CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease, 10.1152/ajprenal.00038.2009
Ammer Amanda Gatesman, Weed Scott A., Cortactin branches out: Roles in regulating protrusive actin dynamics, 10.1002/cm.20296
McNiven Mark A., Kim Leung, Krueger Eugene W., Orth James D., Cao Hong, Wong Tai Wai, Regulated Interactions between Dynamin and the Actin-Binding Protein Cortactin Modulate Cell Shape, 10.1083/jcb.151.1.187
Cao Cong, Lu Shan, Jiang Qin, Wang Wen-jun, Song Xiuzu, Kivlin Rebecca, Wallin Brittany, Bagdasarian Andrew, Tamakloe Tyrone, Chu Wen-ming, EGFR activation confers protections against UV-induced apoptosis in cultured mouse skin dendritic cells, 10.1016/j.cellsig.2008.06.010
Ullrich O., Rab11 regulates recycling through the pericentriolar recycling endosome, 10.1083/jcb.135.4.913
Moestrup, J Biol Chem, 268, 16564 (1993)
Bouchard Maxime, Souabni Abdallah, Busslinger Meinrad, Tissue-specific expression of cre recombinase from thePax8 locus, 10.1002/gene.20008
Bibliographic reference
Carpentier, Sarah ; N'Kuli, Francisca ; Grieco, Giuseppina ; Van Der Smissen, Patrick ; Janssens, Virginie ; et. al. Class III phosphoinositide 3-kinase/VPS34 and dynamin are critical for apical endocytic recycling.. In: Traffic, Vol. 14, no. 8, p. 933-948 (2013)
