Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases

Journal of Cell Biology - Tập 167 Số 6 - Trang 1195-1204 - 2004
Xiangbin Kong1, Fang‐Ming Deng1,2, Ping Hu1, Feng‐Xia Liang1, Ge Zhou1, Anna B. Auerbach3, Nancy B. Genieser4, Peter Kim Nelson4, Elizabeth Robbins5, Ellen Shapiro2, Bechara Kachar6, Tung‐Tien Sun1,2,7,8
11Epithelial Biology Unit, The Ronald O. Perelman Department of Dermatology
22Department of Urology.
36Skirball Institute of Biomolecular Medicine
43Department of Radiology
54Department of Cell Biology
68Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892
75Department of Pharmacology
87and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016

Tóm tắt

The apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

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Tài liệu tham khảo

2000, Invest. Ophthalmol. Vis. Sci., 41, 2900

2004, Traffic., 5, 117, 10.1046/j.1600-0854.2003.00156.x

2001, J. Cell Sci., 114, 4143, 10.1242/jcs.114.23.4143

2001, Cell. Mol. Life Sci., 58, 1189, 10.1007/PL00000933

1983, J. Mol. Biol., 166, 21, 10.1016/S0022-2836(83)80048-5

2003, Proc. Natl. Acad. Sci. USA., 100, 14012, 10.1073/pnas.2436350100

1996, J. Urol., 155, 1139, 10.1016/S0022-5347(01)66407-3

1985, Lab. Invest., 52, 243

2002, J. Cell Biol., 159, 685, 10.1083/jcb.200204102

2004, Histochem. Cell Biol., 121, 63, 10.1007/s00418-003-0600-x

1975, Virchows Arch. B Cell Pathol., 18, 35, 10.1007/BF02889232

1976, Virchows Arch. B Cell Pathol., 21, 279, 10.1007/BF02899161

1978, Virchows Arch. B Cell Pathol., 26, 215, 10.1007/BF02889549

2003, Hum. Mol. Genet., 12, 631, 10.1093/hmg/ddg062

2004, J. Urol., 171, 931, 10.1097/01.ju.0000094802.50650.3d

2001, J. Cell Biol., 155, 1103, 10.1083/jcb.200108061

2003, Annu. Rev. Cell Dev. Biol., 19, 397, 10.1146/annurev.cellbio.19.111301.153609

1965, J. Cell Biol., 26, 25, 10.1083/jcb.26.1.25

1975, Biol. Rev. Camb. Philos. Soc., 50, 215, 10.1111/j.1469-185X.1975.tb01057.x

1969, Nature., 224, 1304, 10.1038/2241304a0

1999, BJU Int., 83, 318, 10.1046/j.1464-410x.1999.00923.x

2000, J. Cell Biol., 151, 961, 10.1083/jcb.151.5.961

2002, Am. J. Physiol. Renal Physiol., 283, F1200, 10.1152/ajprenal.00043.2002

2004, Kidney Int., 66, 10, 10.1111/j.1523-1755.2004.00703.x

1999, J. Mol. Biol., 285, 595, 10.1006/jmbi.1998.2304

1991, Mol. Cell. Biol., 11, 5338

1969, Lab. Invest., 21, 154

1990, Biochem. Biophys. Res. Commun., 173, 902, 10.1016/S0006-291X(05)80871-X

1998, Annu. Rev. Immunol., 16, 89, 10.1146/annurev.immunol.16.1.89

2000, Am. J. Physiol. Renal Physiol., 278, F867, 10.1152/ajprenal.2000.278.6.F867

1982, Nature., 297, 685, 10.1038/297685a0

1999, Differentiation., 65, 59, 10.1046/j.1432-0436.1999.6510059.x

2001, Biochem. J., 355, 13, 10.1042/bj3550013

1994, J. Biol. Chem., 269, 1775, 10.1016/S0021-9258(17)42095-3

1997, FASEB J., 11, 428, 10.1096/fasebj.11.6.9194523

2003, Curr. Opin. Pediatr., 15, 181, 10.1097/00008480-200304000-00007

1972, J. Anat., 112, 433

1981, Acta Anat. (Basel)., 110, 359, 10.1159/000145447

2003, J. Urol., 170, 1628, 10.1097/01.ju.0000084407.24615.f8

2003, J. Cell Sci., 116, 4087, 10.1242/jcs.00811

1992, J. Urol., 148, 158, 10.1016/S0022-5347(17)36544-8

1996, Am. J. Physiol., 271, F886

1999, Mol. Cell., 3, 1, 10.1016/S1097-2765(00)80169-0

2003, J. Pathol., 199, 41, 10.1002/path.1252

2001, J. Mol. Biol., 314, 245, 10.1006/jmbi.2001.5128

1995, J. Biol. Chem., 270, 27954, 10.1074/jbc.270.46.27954

1994, J. Pathol., 173, 283, 10.1002/path.1711730312

2001, Methods Mol. Biol., 158, 217

1998, Pharmacol. Rev., 50, 683

1989, Differentiation., 42, 103, 10.1111/j.1432-0436.1989.tb00611.x

2002, Arch. Dis. Child., 87, 114, 10.1136/adc.87.2.114

1979, J. Ultrastruct. Res., 69, 279, 10.1016/S0022-5320(79)90117-5

1972, J. Cell Biol., 53, 73, 10.1083/jcb.53.1.73

1999, Adv. Exp. Med. Biol., 462, 7, 10.1007/978-1-4615-4737-2_1

1990, J. Cell Sci., 97, 419, 10.1242/jcs.97.3.419

2003, Trends Immunol., 24, 610, 10.1016/j.it.2003.09.011

2002, Mol. Biol. Cell., 13, 830, 10.1091/mbc.01-09-0435

1982, Cell., 30, 361, 10.1016/0092-8674(82)90234-3

2002, Mol. Biol. Cell., 13, 4221, 10.1091/mbc.e02-04-0211

2004, J. Cell Sci., 117, 2029, 10.1242/jcs.01042

2004, Eur. J. Cell Biol., 83, 27, 10.1078/0171-9335-00351

1969, J. Mol. Biol., 46, 593, 10.1016/0022-2836(69)90200-9

1995, J. Mol. Biol., 248, 887, 10.1006/jmbi.1995.0269

1984, J. Cell Biol., 98, 1397, 10.1083/jcb.98.4.1397

2002, Trends Neurosci., 25, 336, 10.1016/S0166-2236(02)02192-6

1993, J. Cell Sci., 106, 31, 10.1242/jcs.106.1.31

1994, J. Biol. Chem., 269, 13716, 10.1016/S0021-9258(17)36889-8

1995, J. Biol. Chem., 270, 29752, 10.1074/jbc.270.50.29752

2002, J. Urol., 168, 1138, 10.1016/S0022-5347(05)64611-3

1994, J. Cell Biol., 125, 171, 10.1083/jcb.125.1.171

2003, Cell. Signal., 15, 559, 10.1016/S0898-6568(02)00147-X

1996, Am. J. Physiol., 271, F243

2001, J. Cell Sci., 114, 4095, 10.1242/jcs.114.22.4095

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Thông tin xuất bản

Journal of Cell Biology

Tập 167 Số 6

1195-1204

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