|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 2003 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 2002 : ¥1,900,000 (Direct Cost : ¥1,900,000)
In normal kidney, the foot processes of podocytes are maintained wide open to facilitate passage of the glomerular filtrate, and they are held together by the specialized cell-cell contact named slit diaphragms. During glomerular development, the junctional complex containing tight junctions between immature podocytes migrates from the apex to the base of the cells, eventually disappeared, and the junctions are replaced by slit diaphragms suggesting that the slit diaphragm is a modified cell-cell junction. Recently, we have localized another tight junction protein, ASIP/PAR3, which interacts with atypical protein kinase C isotypes and plays a crucial role in the establishment of polarity in various cells. ASIP/PAR3 was detected at the base of slit diaphragms. In developing kidney, the signal for ASIP/PAR3 appeared at the tight junction between podocytes and coincided with that for ZO-1 during differentiation. Adherens junction molecules including cadherins, catenins and afadin disappea
red during maturation of podocyte. In addition, we have cloned rat podocin, a new member of slit membrane proteins.
The foot processes of podocytes abundantly possess microfilaments. We investigated the actin filament organization of foot processes in adult rat podocytes as well as the formation of actin cytoskeletal system of immature podocytes during glomerulogenesis. Electron microscopy revealed two populations of actin cytoskeleton in foot processes of adult podocytes, one is the actin bundle running above the level of slit diaphragms, the other is the cortical actin network located beneath the plasmalemma. Immunogold labeling for actin-binding proteins demonstrated that alpha-actinin and synaptopodin were localized in the actin bundle, whereas cortactin was in the cortical actin network. We conclude that foot processes have specialized actin filamentous organization and its establishment is associated with the expression and redistribution of actin-binding proteins during development. We also found a novel protein, Vmac, associated with vimentin-type intermediate filaments in podocytes of rat kidney. Less