Apical-basal polarity regulators are essential for slit diaphragm assembly and endocytosis in Drosophila nephrocytes.
Expansion microscopy
Nephrocyte
PAR-1
PAR-3
Podocyte
Polarity
Slit diaphragm
aPKC
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
28
04
2020
accepted:
16
01
2021
revised:
11
01
2021
pubmed:
3
3
2021
medline:
28
4
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
Apical-basal polarity is a key feature of most epithelial cells and it is regulated by highly conserved protein complexes. In mammalian podocytes, which emerge from columnar epithelial cells, this polarity is preserved and the tight junctions are converted to the slit diaphragms, establishing the filtration barrier. In Drosophila, nephrocytes show several structural and functional similarities with mammalian podocytes and proximal tubular cells. However, in contrast to podocytes, little is known about the role of apical-basal polarity regulators in these cells. In this study, we used expansion microscopy and found the apical polarity determinants of the PAR/aPKC and Crb-complexes to be predominantly targeted to the cell cortex in proximity to the nephrocyte diaphragm, whereas basolateral regulators also accumulate intracellularly. Knockdown of PAR-complex proteins results in severe endocytosis and nephrocyte diaphragm defects, which is due to impaired aPKC recruitment to the plasma membrane. Similar, downregulation of most basolateral polarity regulators disrupts Nephrin localization but had surprisingly divergent effects on endocytosis. Our findings suggest that morphology and slit diaphragm assembly/maintenance of nephrocytes is regulated by classical apical-basal polarity regulators, which have distinct functions in endocytosis.
Identifiants
pubmed: 33651172
doi: 10.1007/s00018-021-03769-y
pii: 10.1007/s00018-021-03769-y
pmc: PMC8038974
doi:
Substances chimiques
Drosophila Proteins
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
baz protein, Drosophila
0
nephrin
0
PKC-3 protein
EC 2.7.11.13
Protein Kinase C
EC 2.7.11.13
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3657-3672Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1348-A05
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1348-A03
Références
Weavers H, Prieto-Sanchez S, Grawe F, Garcia-Lopez A, Artero R, Wilsch-Brauninger M, Ruiz-Gomez M, Skaer H, Denholm B (2009) The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm. Nature 457(7227):322–326. https://doi.org/10.1038/nature07526
doi: 10.1038/nature07526
pubmed: 18971929
Zhuang S, Shao H, Guo F, Trimble R, Pearce E, Abmayr SM (2009) Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes. Development 136(14):2335–2344. https://doi.org/10.1242/dev.031609
doi: 10.1242/dev.031609
pubmed: 19515699
pmcid: 2729346
Hochapfel F, Denk L, Maassen C, Zaytseva Y, Rachel R, Witzgall R, Krahn MP (2018) Electron microscopy of drosophila garland cell nephrocytes: optimal preparation, immunostaining and STEM tomography. J Cell Biochem. https://doi.org/10.1002/jcb.26702
doi: 10.1002/jcb.26702
pubmed: 29380411
Zhang F, Zhao Y, Chao Y, Muir K, Han Z (2013) Cubilin and amnionless mediate protein reabsorption in Drosophila nephrocytes. J Am Soc Nephrol JASN 24(2):209–216. https://doi.org/10.1681/ASN.2012080795
doi: 10.1681/ASN.2012080795
pubmed: 23264686
Hochapfel F, Denk L, Mendl G, Schulze U, Maassen C, Zaytseva Y, Pavenstadt H, Weide T, Rachel R, Witzgall R, Krahn MP (2017) Distinct functions of Crumbs regulating slit diaphragms and endocytosis in Drosophila nephrocytes. Cell Mol Life Sci CMLS 74(24):4573–4586. https://doi.org/10.1007/s00018-017-2593-y
doi: 10.1007/s00018-017-2593-y
pubmed: 28717874
Weide T, Vollenbroker B, Schulze U, Djuric I, Edeling M, Bonse J, Hochapfel F, Panichkina O, Wennmann DO, George B, Kim S, Daniel C, Seggewiss J, Amann K, Kriz W, Krahn MP, Pavenstadt H (2017) Pals1 haploinsufficiency results in proteinuria and cyst formation. J Am Soc Nephrol JASN 28(7):2093–2107. https://doi.org/10.1681/ASN.2016040474
doi: 10.1681/ASN.2016040474
pubmed: 28154200
Ebarasi L, Ashraf S, Bierzynska A, Gee HY, McCarthy HJ, Lovric S, Sadowski CE, Pabst W, Vega-Warner V, Fang H, Koziell A, Simpson MA, Dursun I, Serdaroglu E, Levy S, Saleem MA, Hildebrandt F, Majumdar A (2015) Defects of CRB2 cause steroid-resistant nephrotic syndrome. Am J Hum Genet 96(1):153–161. https://doi.org/10.1016/j.ajhg.2014.11.014
doi: 10.1016/j.ajhg.2014.11.014
pubmed: 25557779
pmcid: 4289689
Slavotinek A, Kaylor J, Pierce H, Cahr M, DeWard SJ, Schneidman-Duhovny D, Alsadah A, Salem F, Schmajuk G, Mehta L (2015) CRB2 mutations produce a phenotype resembling congenital nephrosis, Finnish type, with cerebral ventriculomegaly and raised alpha-fetoprotein. Am J Hum Genet 96(1):162–169. https://doi.org/10.1016/j.ajhg.2014.11.013
doi: 10.1016/j.ajhg.2014.11.013
pubmed: 25557780
pmcid: 4289687
Odenthal J, Brinkkoetter PT (2019) Drosophila melanogaster and its nephrocytes: a versatile model for glomerular research. Methods Cell Biol 154:217–240. https://doi.org/10.1016/bs.mcb.2019.03.011
doi: 10.1016/bs.mcb.2019.03.011
pubmed: 31493819
Helmstadter M, Huber TB, Hermle T (2017) Using the drosophila nephrocyte to model podocyte function and disease. Front Pediatr 5:262. https://doi.org/10.3389/fped.2017.00262
doi: 10.3389/fped.2017.00262
pubmed: 29270398
pmcid: 5725439
Helmstadter M, Simons M (2017) Using Drosophila nephrocytes in genetic kidney disease. Cell Tissue Res 369(1):119–126. https://doi.org/10.1007/s00441-017-2606-z
doi: 10.1007/s00441-017-2606-z
pubmed: 28401308
Kampf LL, Schneider R, Gerstner L, Thunauer R, Chen M, Helmstadter M, Amar A, Onuchic-Whitford AC, Loza Munarriz R, Berdeli A, Muller D, Schrezenmeier E, Budde K, Mane S, Laricchia KM, Rehm HL, MacArthur DG, Lifton RP, Walz G, Romer W, Bergmann C, Hildebrandt F, Hermle T (2019) TBC1D8B mutations implicate RAB11-dependent vesicular trafficking in the pathogenesis of nephrotic syndrome. J Am Soc Nephrol JASN 30(12):2338–2353. https://doi.org/10.1681/ASN.2019040414
doi: 10.1681/ASN.2019040414
pubmed: 31732614
Hermle T, Schneider R, Schapiro D, Braun DA, van der Ven AT, Warejko JK, Daga A, Widmeier E, Nakayama M, Jobst-Schwan T, Majmundar AJ, Ashraf S, Rao J, Finn LS, Tasic V, Hernandez JD, Bagga A, Jalalah SM, El Desoky S, Kari JA, Laricchia KM, Lek M, Rehm HL, MacArthur DG, Mane S, Lifton RP, Shril S, Hildebrandt F (2018) GAPVD1 and ANKFY1 mutations implicate RAB5 regulation in nephrotic syndrome. J Am Soc Nephrol JASN. https://doi.org/10.1681/ASN.2017121312
doi: 10.1681/ASN.2017121312
pubmed: 30143558
Gee HY, Zhang F, Ashraf S, Kohl S, Sadowski CE, Vega-Warner V, Zhou W, Lovric S, Fang H, Nettleton M, Zhu JY, Hoefele J, Weber LT, Podracka L, Boor A, Fehrenbach H, Innis JW, Washburn J, Levy S, Lifton RP, Otto EA, Han Z, Hildebrandt F (2015) KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. J Clin Investig 125(6):2375–2384. https://doi.org/10.1172/JCI79504
doi: 10.1172/JCI79504
pubmed: 25961457
Hermle T, Braun DA, Helmstadter M, Huber TB, Hildebrandt F (2017) Modeling monogenic human nephrotic syndrome in the drosophila garland cell nephrocyte. J Am Soc Nephrol JASN 28(5):1521–1533. https://doi.org/10.1681/ASN.2016050517
doi: 10.1681/ASN.2016050517
pubmed: 27932481
Fu Y, Zhu JY, Richman A, Zhao Z, Zhang F, Ray PE, Han Z (2017) A Drosophila model system to assess the function of human monogenic podocyte mutations that cause nephrotic syndrome. Hum Mol Genet 26(4):768–780. https://doi.org/10.1093/hmg/ddw428
doi: 10.1093/hmg/ddw428
pubmed: 28164240
pmcid: 6074792
Kruzel-Davila E, Shemer R, Ofir A, Bavli-Kertselli I, Darlyuk-Saadon I, Oren-Giladi P, Wasser WG, Magen D, Zaknoun E, Schuldiner M, Salzberg A, Kornitzer D, Marelja Z, Simons M, Skorecki K (2017) APOL1-mediated cell injury involves disruption of conserved trafficking processes. J Am Soc Nephrol JASN 28(4):1117–1130. https://doi.org/10.1681/ASN.2016050546
doi: 10.1681/ASN.2016050546
pubmed: 27864431
Fu Y, Zhu JY, Richman A, Zhang Y, Xie X, Das JR, Li J, Ray PE, Han Z (2017) APOL1-G1 in nephrocytes induces hypertrophy and accelerates cell death. J Am Soc Nephrol JASN 28(4):1106–1116. https://doi.org/10.1681/ASN.2016050550
doi: 10.1681/ASN.2016050550
pubmed: 27864430
Hartley PS, Motamedchaboki K, Bodmer R, Ocorr K (2016) SPARC-dependent cardiomyopathy in drosophila. Circ Cardiovasc Genet 9(2):119–129. https://doi.org/10.1161/CIRCGENETICS.115.001254
doi: 10.1161/CIRCGENETICS.115.001254
pubmed: 26839388
pmcid: 4838489
Troha K, Nagy P, Pivovar A, Lazzaro BP, Hartley PS, Buchon N (2019) Nephrocytes remove microbiota-derived peptidoglycan from systemic circulation to maintain immune homeostasis. Immunity 51(4):625–637. https://doi.org/10.1016/j.immuni.2019.08.020
doi: 10.1016/j.immuni.2019.08.020
pubmed: 31564469
Na J, Sweetwyne MT, Park AS, Susztak K, Cagan RL (2015) Diet-induced podocyte dysfunction in drosophila and mammals. Cell Rep 12(4):636–647. https://doi.org/10.1016/j.celrep.2015.06.056
doi: 10.1016/j.celrep.2015.06.056
pubmed: 26190114
pmcid: 4532696
Itoh M, Nakadate K, Horibata Y, Matsusaka T, Xu J, Hunziker W, Sugimoto H (2014) The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1. PLoS ONE 9(9):e106621. https://doi.org/10.1371/journal.pone.0106621
doi: 10.1371/journal.pone.0106621
pubmed: 25184792
pmcid: 4153657
Huber TB, Schmidts M, Gerke P, Schermer B, Zahn A, Hartleben B, Sellin L, Walz G, Benzing T (2003) The carboxyl terminus of Neph family members binds to the PDZ domain protein zonula occludens-1. J Biol Chem 278(15):13417–13421. https://doi.org/10.1074/jbc.C200678200
doi: 10.1074/jbc.C200678200
pubmed: 12578837
Carrasco-Rando M, Prieto-Sanchez S, Culi J, Tutor AS, Ruiz-Gomez M (2019) A specific isoform of Pyd/ZO-1 mediates junctional remodeling and formation of slit diaphragms. J Cell Biol 218(7):2294–2308. https://doi.org/10.1083/jcb.201810171
doi: 10.1083/jcb.201810171
pubmed: 31171632
pmcid: 6605796
Hirose T, Satoh D, Kurihara H, Kusaka C, Hirose H, Akimoto K, Matsusaka T, Ichikawa I, Noda T, Ohno S (2009) An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms. PLoS ONE 4(1):e4194. https://doi.org/10.1371/journal.pone.0004194
doi: 10.1371/journal.pone.0004194
pubmed: 19142224
pmcid: 2614475
Hartleben B, Schweizer H, Lubben P, Bartram MP, Moller CC, Herr R, Wei C, Neumann-Haefelin E, Schermer B, Zentgraf H, Kerjaschki D, Reiser J, Walz G, Benzing T, Huber TB (2008) Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity. J Biol Chem 283(34):23033–23038. https://doi.org/10.1074/jbc.M803143200
doi: 10.1074/jbc.M803143200
pubmed: 18562307
pmcid: 2516981
Huber TB, Hartleben B, Winkelmann K, Schneider L, Becker JU, Leitges M, Walz G, Haller H, Schiffer M (2009) Loss of podocyte aPKClambda/iota causes polarity defects and nephrotic syndrome. J Am Soc Nephrol JASN 20(4):798–806. https://doi.org/10.1681/ASN.2008080871
doi: 10.1681/ASN.2008080871
pubmed: 19279126
Satoh D, Hirose T, Harita Y, Daimon C, Harada T, Kurihara H, Yamashita A, Ohno S (2014) aPKClambda maintains the integrity of the glomerular slit diaphragm through trafficking of nephrin to the cell surface. J Biochem 156(2):115–128. https://doi.org/10.1093/jb/mvu022
doi: 10.1093/jb/mvu022
pubmed: 24700503
pmcid: 4112437
Hartleben B, Widmeier E, Suhm M, Worthmann K, Schell C, Helmstadter M, Wiech T, Walz G, Leitges M, Schiffer M, Huber TB (2013) aPKClambda/iota and aPKCzeta contribute to podocyte differentiation and glomerular maturation. J Am Soc Nephrol JASN 24(2):253–267. https://doi.org/10.1681/ASN.2012060582
doi: 10.1681/ASN.2012060582
pubmed: 23334392
Koehler S, Tellkamp F, Niessen CM, Bloch W, Kerjaschki D, Schermer B, Benzing T, Brinkkoetter PT (2016) Par3A is dispensable for the function of the glomerular filtration barrier of the kidney. Am J Physiol Renal Physiol 311(1):F112-119. https://doi.org/10.1152/ajprenal.00171.2016
doi: 10.1152/ajprenal.00171.2016
pubmed: 27122542
Tepass U (2012) The apical polarity protein network in Drosophila epithelial cells: regulation of polarity, junctions, morphogenesis, cell growth, and survival. Annu Rev Cell Dev Biol 28:655–685. https://doi.org/10.1146/annurev-cellbio-092910-154033
doi: 10.1146/annurev-cellbio-092910-154033
pubmed: 22881460
Campanale JP, Sun TY, Montell DJ (2017) Development and dynamics of cell polarity at a glance. J Cell Sci 130(7):1201–1207. https://doi.org/10.1242/jcs.188599
doi: 10.1242/jcs.188599
pubmed: 28365593
pmcid: 5399778
Rodriguez-Boulan E, Macara IG (2014) Organization and execution of the epithelial polarity programme. Nat Rev Mol Cell Biol 15(4):225–242. https://doi.org/10.1038/nrm3775
doi: 10.1038/nrm3775
pubmed: 24651541
pmcid: 4211427
Doerflinger H, Vogt N, Torres IL, Mirouse V, Koch I, Nusslein-Volhard C, St Johnston D (2010) Bazooka is required for polarisation of the Drosophila anterior-posterior axis. Development 137(10):1765–1773. https://doi.org/10.1242/dev.045807
doi: 10.1242/dev.045807
pubmed: 20430751
pmcid: 2860254
Dogliotti G, Kullmann L, Dhumale P, Thiele C, Panichkina O, Mendl G, Houben R, Haferkamp S, Puschel AW, Krahn MP (2017) Membrane-binding and activation of LKB1 by phosphatidic acid is essential for development and tumour suppression. Nature Commun 8:15747. https://doi.org/10.1038/ncomms15747
doi: 10.1038/ncomms15747
Sotillos S, Diaz-Meco MT, Caminero E, Moscat J, Campuzano S (2004) DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila. J Cell Biol 166(4):549–557
doi: 10.1083/jcb.200311031
Feng Y, Ueda A, Wu CF (2004) A modified minimal hemolymph-like solution, HL3.1, for physiological recordings at the neuromuscular junctions of normal and mutant Drosophila larvae. J Neurogenet 18(2):377–402. https://doi.org/10.1080/01677060490894522
doi: 10.1080/01677060490894522
pubmed: 15763995
Kullmann L, Krahn MP (2018) Redundant regulation of localization and protein stability of DmPar3. Cell Mol Life Sci CMLS 75(17):3269–3282. https://doi.org/10.1007/s00018-018-2792-1
doi: 10.1007/s00018-018-2792-1
pubmed: 29523893
Kim S, Gailite I, Moussian B, Luschnig S, Goette M, Fricke K, Honemann-Capito M, Grubmuller H, Wodarz A (2009) Kinase-activity-independent functions of atypical protein kinase C in Drosophila. J Cell Sci 122(Pt 20):3759–3771
doi: 10.1242/jcs.052514
Khaliullina H, Panakova D, Eugster C, Riedel F, Carvalho M, Eaton S (2009) Patched regulates smoothened trafficking using lipoprotein-derived lipids. Development 136(24):4111–4121. https://doi.org/10.1242/dev.041392
doi: 10.1242/dev.041392
pubmed: 19906846
Sen A, Nagy-Zsver-Vadas Z, Krahn MP (2012) Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity. J Cell Biol 199(4):685–698. https://doi.org/10.1083/jcb.201206064
doi: 10.1083/jcb.201206064
pubmed: 23128243
pmcid: 3494860
Tanaka T, Nakamura A (2008) The endocytic pathway acts downstream of Oskar in Drosophila germ plasm assembly. Development 135(6):1107–1117. https://doi.org/10.1242/dev.017293
doi: 10.1242/dev.017293
pubmed: 18272590
Berger S, Bulgakova NA, Grawe F, Johnson K, Knust E (2007) Unraveling the genetic complexity of Drosophila stardust during photoreceptor morphogenesis and prevention of light-induced degeneration. Genetics 176(4):2189–2200
doi: 10.1534/genetics.107.071449
Chen F, Tillberg PW, Boyden ES (2015) Optical imaging. expansion microscopy. Science 347(6221):543–548. https://doi.org/10.1126/science.1260088
doi: 10.1126/science.1260088
pubmed: 25592419
pmcid: 4312537
Chozinski TJ, Mao C, Halpern AR, Pippin JW, Shankland SJ, Alpers CE, Najafian B, Vaughan JC (2018) Volumetric, nanoscale optical imaging of mouse and human kidney via expansion microscopy. Sci Rep 8(1):10396. https://doi.org/10.1038/s41598-018-28694-2
doi: 10.1038/s41598-018-28694-2
pubmed: 29991751
pmcid: 6039510
Sen A, Sun R, Krahn MP (2015) Localization and function of pals1-associated tight junction protein in drosophila is regulated by two distinct apical complexes. J Biol Chem 290(21):13224–13233. https://doi.org/10.1074/jbc.M114.629014
doi: 10.1074/jbc.M114.629014
pubmed: 25847234
pmcid: 4505576
Benton R, St Johnston D (2003) Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell 115(6):691–704
doi: 10.1016/S0092-8674(03)00938-3
Hutterer A, Betschinger J, Petronczki M, Knoblich JA (2004) Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev Cell 6(6):845–854
doi: 10.1016/j.devcel.2004.05.003
Krahn MP, Egger-Adam D, Wodarz A (2009) PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts. Dev Cell 16(6):901–908
doi: 10.1016/j.devcel.2009.04.011
Zhang F, Zhao Y, Han Z (2013) An in vivo functional analysis system for renal gene discovery in Drosophila pericardial nephrocytes. J Am Soc Nephrol JASN 24(2):191–197. https://doi.org/10.1681/ASN.2012080769
doi: 10.1681/ASN.2012080769
pubmed: 23291470
Kim S, Wairkar YP, Daniels RW, DiAntonio A (2010) The novel endosomal membrane protein Ema interacts with the class C Vps-HOPS complex to promote endosomal maturation. J Cell Biol 188(5):717–734. https://doi.org/10.1083/jcb.200911126
doi: 10.1083/jcb.200911126
pubmed: 20194640
pmcid: 2835942
Lorincz P, Lakatos Z, Varga A, Maruzs T, Simon-Vecsei Z, Darula Z, Benko P, Csordas G, Lippai M, Ando I, Hegedus K, Medzihradszky KF, Takats S, Juhasz G (2016) MiniCORVET is a Vps8-containing early endosomal tether in Drosophila. eLife. https://doi.org/10.7554/eLife.14226
doi: 10.7554/eLife.14226
pubmed: 27253064
pmcid: 4935465
Lund VK, Madsen KL, Kjaerulff O (2018) Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes. Autophagy 14(9):1520–1542. https://doi.org/10.1080/15548627.2018.1458170
doi: 10.1080/15548627.2018.1458170
pubmed: 29940804
pmcid: 6135592
Wodarz A, Ramrath A, Grimm A, Knust E (2000) Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol 150(6):1361–1374
doi: 10.1083/jcb.150.6.1361
Holly RW, Jones K, Prehoda KE (2020) A conserved PDZ-binding motif in aPKC interacts with Par-3 and Mediates cortical polarity. Curr Biol. https://doi.org/10.1016/j.cub.2019.12.055
doi: 10.1016/j.cub.2019.12.055
pubmed: 32084408
pmcid: 7104911
Renschler FA, Bruekner SR, Salomon PL, Mukherjee A, Kullmann L, Schutz-Stoffregen MC, Henzler C, Pawson T, Krahn MP, Wiesner S (2018) Structural basis for the interaction between the cell polarity proteins Par3 and Par6. Sci Signal. https://doi.org/10.1126/scisignal.aam9899
doi: 10.1126/scisignal.aam9899
pubmed: 29440511
Nagai-Tamai Y, Mizuno K, Hirose T, Suzuki A, Ohno S (2002) Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells. Genes Cells 7(11):1161–1171
doi: 10.1046/j.1365-2443.2002.00590.x
Krahn MP, Buckers J, Kastrup L, Wodarz A (2010) Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia. J Cell Biol 190(5):751–760. https://doi.org/10.1083/jcb.201006029
doi: 10.1083/jcb.201006029
pubmed: 20819933
pmcid: 2935580
Gleixner EM, Canaud G, Hermle T, Guida MC, Kretz O, Helmstadter M, Huber TB, Eimer S, Terzi F, Simons M (2014) V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis. Cell Rep 8(1):10–19. https://doi.org/10.1016/j.celrep.2014.05.035
doi: 10.1016/j.celrep.2014.05.035
pubmed: 24953654
Toshima JY, Nishinoaki S, Sato Y, Yamamoto W, Furukawa D, Siekhaus DE, Sawaguchi A, Toshima J (2014) Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole. Nature Commun. https://doi.org/10.1038/Ncomms4498
doi: 10.1038/Ncomms4498
Hartleben B, Widmeier E, Wanner N, Schmidts M, Kim ST, Schneider L, Mayer B, Kerjaschki D, Miner JH, Walz G, Huber TB (2012) Role of the polarity protein Scribble for podocyte differentiation and maintenance. PLoS ONE 7(5):e36705. https://doi.org/10.1371/journal.pone.0036705
doi: 10.1371/journal.pone.0036705
pubmed: 22586490
pmcid: 3346764
Portela M, Parsons LM, Grzeschik NA, Richardson HE (2015) Regulation of Notch signaling and endocytosis by the Lgl neoplastic tumor suppressor. Cell Cycle 14(10):1496–1506. https://doi.org/10.1080/15384101.2015.1026515
doi: 10.1080/15384101.2015.1026515
pubmed: 25789785
pmcid: 4613855
Parsons LM, Portela M, Grzeschik NA, Richardson HE (2014) Lgl regulates Notch signaling via endocytosis, independently of the apical aPKC-Par6-Baz polarity complex. Curr Biol 24(18):2073–2084. https://doi.org/10.1016/j.cub.2014.07.075
doi: 10.1016/j.cub.2014.07.075
pubmed: 25220057