Research Summary:

The study of proteins that control epithelial cell polarity and tight junction formation. The work focuses on large protein complexes that are present at the tight junction and control initial epithelial cell polarization. These protein complexes may also be important for slit diaphragm formation in the glomerulus. Additionally several proteins in this complex are involved in the formation of cilia at the apical surface of epithelial cells. Defects in ciliogenesis have been implicated in polycystic kidney disease. Trainees in the laboratory will be involved in these projects training in epithelial biology, molecular techniques and protein biochemistry.

Link to PubMed Citations

Selected Publications:

Margolis, B and Traub, LM. PTB Domains in Cesareni, G., Gimona, M., Sudol, M, Yaffe, M. (Eds). Modular Protein Domains. Wiley-VCH, Wernheim, 2005.

Margolis B, Borg JP. Polarity Complexes. J Cell Sci. 118:5157-9, 2005.

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. 280:33580-7, 2005.

Latorre IJ, Roh MH, Frese KK, Weiss RS, Margolis B, Javier RT. Viral oncoprotein-induced mislocalization of select PDZ proteins disrupts tight junctions and causes polarity defects in epithelial cells. J Cell Sci. 118:4283-93, 2005.

Fogg, VC, Liu, CJ, and Margolis, B. Multiple regions of Crumbs3 are required for tight junction formation in MCF10A cells. J. Cell. Sci., 118:2859-69, 2005

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. 37:282-8, 2005.

Shin, K, Straight S. and Margolis, B. PATJ Regulates Tight Junction Formation and Polarity in Mammalian Epithelial Cells. J. Cell Biol, 168:705-11, 2005

Fan S., Hurd T.W., Liu C.J., Straight S.W., Weimbs T., Hurd E.A, Domino S.E. and Margolis B. Polarity proteins control ciliogenesis via kinesin motor interactions. Curr. Biol, 14:1451-61, 2004.

Li Y., Karnak D., Demeler B., Margolis B. and Lavie A. Structural basis for L27 domain-mediated assembly of signaling and cell polarity complexes. EMBO J. 23:2723-33, 2004.

Wang Q., Hurd T.W., and Margolis B. Tight junction protein Par6 interacts with an evolutionarily conserved region in the amino-terminus of PALS1/stardust. J Biol Chem. 279:30715-21, 2004.

Straight, S.W., Shin K., Fogg V.C., Fan S., Liu C.J., Roh M., and Margolis B. Loss of PALS1 expression leads to tight junction and polarity defects. Mol Biol Cell. 15:1981-90, 2004.

Hurd, T.W., Fan, S., Liu, C-J., Kweon, HY, Hakansson, K., and Margolis B. Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia. Current Biology, 13:2082-90, 2003.

Roh M.H., Fan S., Liu, C-J. and Margolis, B. The Crumbs3/Pals1 Complex Participates in the Establishment of Polarity in Mammalian Epithelial Cells. J. Cell Sci., 116:2895-906, 2003.

Hurd TW, Gao L, Roh MH, Macara IG, and Margolis B. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat Cell Biol. 5:137-42, 2003.

Makarova O., Roh M.H., Liu C-J., Laurinec S. and Margolis B. Mammalian Crumbs3 is a small transmembrane protein linked to Pals1. Gene, 302:21-9, 2003.

Karnak D. and Margolis B. Identification of multiple binding partners for the amino-terminal domain of SAP97. J. Biol. Chem. 277:46730-5, 2002.

Patrie KM, Drescher AJ, Welihinda A, Mundel P and Margolis B. Interaction of two actin-binding proteins, synaptopodin and a-actinin-4, with the tight junction protein MAGI-1. J Biol Chem. 277:30183-90, 2002.

Roh MH, Liu CJ, Laurinec S and Margolis B. The carboxy-terminus of Zona Occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions. J Biol Chem. 277:27501-9, 2002.

Roh M.H., Makarova O., Liu C., Shin KY, Lee S., Laurinec S., Goyal M., Wiggins R. and Margolis B. The Maguk protein, Pals1, function as an adapter linking mammalian homologues of Crumbs and Discs Lost. J. Cell Biol. 157: 161-172, 2002.

Lee S., Fan S., Makarova O., Liu C., Straight S. and Margolis B. A novel and conserved protein-protein interaction domain of mLin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia. Mol. Cell Biol. 22: 1778-1791, 2002.

Straight S.W., Chen L., Karnak D. and Margolis B. Interactions with mLin-7 alters the targeting of endocytosed transmembrane proteins in mammalian epithelial cells. Mol. Biol. Cell 12:1329-1340, 2001.

Patrie K.M., Drescher A.J., Goyal M., Wiggins R.C. and Margolis B. The MAGUK protein MAGI-1 binds megalin and is present in glomerular podocytes. JASN 12:667-677, 2001.

Verhey K.J., Meyer D., Deehan R., Blenis J., Schnapp B.J., Rapoport T.A. and Margolis B. Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol.152:959-970, 2001.

Doerks T., Bork P., Kamberov E., Makarova O., Muecke S. and Margolis B. L27, a novel heterodimerization domain in receptor targeting proteins Lin-2 and Lin-7. TIBS 25:317-318, 2000.

Straight S.W., Karnak D., Borg J-P., Kamberov E., Dare H., Wade J.B. and Margolis B. mLin-7 is localized to the basolateral surface of epithelia via its amino-terminus. Amer J. Phys. 278/3:F464-475, 2000.

Kamberov E., Makarova O., Roh M., Liu A., Karnak D., Straight S. and Margolis B. Molecular cloning and characterization of Pals, proteins associated with mLin-7. J. Biol. Chem., 275:11425-11431, 2000.