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Vol. 13, Issue 12, 4221-4230, December 2002
§
and¶
*Department of Cell Biology, Much of the lower urinary tract, including the bladder, is lined by
a stratified urothelium forming a highly differentiated, superficial
umbrella cell layer. The apical plasma membrane as well as abundant
cytoplasmic fusiform vesicles of the umbrella cells is covered by
two-dimensional crystals that are formed by four membrane proteins
named uroplakins (UPs) Ia, Ib, II, and III. UPs are synthesized on
membrane-bound polysomes, and after several co- and posttranslational
modifications they assemble into planar crystals in a post-Golgi
vesicular compartment. Distension of the bladder may cause fusiform
vesicles to fuse with the apical plasma membrane. We have investigated
the early stages of uroplakin assembly by expressing the four
uroplakins in 293T cells. Transfection experiments showed that, when
expressed individually, only UPIb can exit from the endoplasmic
reticulum (ER) and move to the plasma membrane, whereas UPII and UPIII
reach the plasma membrane only when they form heterodimeric complexes
with UPIa and UPIb, respectively. Heterodimer formation in the ER was
confirmed by pulse-chase experiment followed by coimmunoprecipitation.
Our results indicate that the initial building blocks for the assembly
of crystalline uroplakin plaques are heterodimeric uroplakin complexes
that form in the ER.
Ronald O. Perelman
Department of Dermatology, Department of Pharmacology,
§Department of Urology, and Kaplan
Comprehensive Cancer Center, New York University, School of Medicine,
New York, New York 10016
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