Dr. Margolis studies protein complexes that regulate epithelial polarization. Epithelia polarization leads to the formation of two distinct cell surfaces referred to as basolateral and apical. These surfaces are separated by a sealing junction called the tight junction. Epithelial polarity is crucial for numerous cellular functions including barrier formation and fluid transport. The loss of epithelial polarity in a process called epithelial to mesenchymal transition is felt to occur in several diseases including cancer and fibrosis. We have focused on a complex of tight junction proteins containing Crumbs3, PALS1 and PATJ that regulates cell polarity and tight junction formation. The laboratory also studies this complex and other related protein complexes in cilia formation. Cilia are microtubule based structures that emanate from the apical surface of cells and are felt to be important in environmental sensing by epithelial cells. Defects in cilia formation and function are felt to contribute to renal cystic disease.
Link to PubMed Citations
Schlüter MA, Margolis B. Apical lumen formation in renal epithelia. J Am Soc Nephrol. 2009 Jul;20(7):1444-52. Epub 2009 Jun 4. Review.
Harder JL, Margolis B. SnapShot: tight and adherens junction signaling. Cell. 2008 Jun 13;133(6):1118, 1118.e1-2. PubMed PMID: 18555786.
Whiteman EL, Liu CJ, Fearon ER, Margolis B. The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes. Oncogene. 2008 Jun 19;27(27):3875-9. Epub 2008 Feb 4.
Wang Q, Margolis B. Apical junctional complexes and cell polarity. Kidney Int. 2007 Dec;72(12):1448-58. Epub 2007 Oct 3. Review.
He S, Parapuram SK, Hurd TW, Behnam B, Margolis B, Swaroop A, Khanna H. Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina: insights into X-linked Retinitis Pigmentosa and associated ciliopathies. Vision Res. 2008 Feb;48(3):366-76. Epub 2007 Sep 27.
Fan S, Fogg V, Wang Q, Chen XW, Liu CJ, Margolis B. A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin beta interactions. J Cell Biol. 2007 Jul 30;178(3):387-98. Epub 2007 Jul 23.
Shin K, Wang Q, Margolis B. PATJ regulates directional migration of mammalian epithelial cells. EMBO Rep. 2007 Feb;8(2):158-64. Epub 2007 Jan 19.
Wang Q, Chen XW, Margolis B. PALS1 regulates E-cadherin trafficking in mammalian epithelial cells. Mol Biol Cell. 2007 Mar;18(3):874-85. Epub 2006 Dec 20.
Straight SW, Pieczynski JN, Whiteman EL, Liu CJ, Margolis B. Mammalian lin-7 stabilizes polarity protein complexes. J Biol Chem. 2006 Dec 8;281(49):37738-47. Epub 2006 Oct 1.
Shin K, Margolis B. ZOning out tight junctions. Cell. 2006 Aug 25;126(4):647-9.
Jenkins PM, Hurd TW, Zhang L, McEwen DP, Brown RL, Margolis B, Verhey KJ, Martens JR. Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17. Curr Biol. 2006 Jun 20;16(12):1211-6.
Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 2006;22:207-35. Review.
Margolis B, Borg JP. Apicobasal polarity complexes. J Cell Sci. 2005 Nov 15;118(Pt 22):5157-9.
Khanna H, Hurd TW, Lillo C, Shu X, Parapuram SK, He S, Akimoto M, Wright AF, Margolis B, Williams DS, Swaroop A. RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. J Biol Chem. 2005 Sep 30;280(39):33580-7. Epub 2005 Jul 25.
Fogg VC, Liu CJ, Margolis B. Multiple regions of Crumbs3 are required for tight junction formation in MCF10A cells. J Cell Sci. 2005 Jul 1;118(Pt 13):2859-69.
Shin K, Straight S, Margolis B. PATJ regulates tight junction formation and polarity in mammalian epithelial cells. J Cell Biol. 2005 Feb 28;168(5):705-11.
Otto EA, Loeys B, Khanna H, Hellemans J, Sudbrak R, Fan S, Muerb U, O'Toole JF, Helou J, Attanasio M, Utsch B, Sayer JA, Lillo C, Jimeno D, Coucke P, De Paepe A, Reinhardt R, Klages S, Tsuda M, Kawakami I, Kusakabe T, Omran H, Imm A, Tippens M, Raymond PA, Hill J, Beales P, He S, Kispert A, Margolis B, Williams DS, Swaroop A, Hildebrandt F. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat Genet. 2005 Mar;37(3):282-8. Epub 2005 Feb 20.
Fan S, Hurd TW, Liu CJ, Straight SW, Weimbs T, Hurd EA, Domino SE, Margolis B. Polarity proteins control ciliogenesis via kinesin motor interactions. Curr Biol. 2004 Aug 24;14(16):1451-61.
Wang Q, Hurd TW, Margolis B. Tight junction protein Par6 interacts with an evolutionarily conserved region in the amino terminus of PALS1/stardust. J Biol Chem. 2004 Jul 16;279(29):30715-21. Epub 2004 May 11.
Straight SW, Shin K, Fogg VC, Fan S, Liu CJ, Roh M, Margolis B. Loss of PALS1 expression leads to tight junction and polarity defects. Mol Biol Cell. 2004 Apr;15(4):1981-90. Epub 2004 Jan 12.