Podocyte Biology and Response to Injury

Abstract

Podocyte FP are not static, but rather contain a contractile system similar to that seen in pericytes. This contractile apparatus is composed of actin, myosin-II, α-actinin-4, talin, and vinculin (1). The actin filament bundles form arches between adjacent FP of the same podocyte (2). Figure 1 is a schema of our current understanding of the molecular composition of the cytoskeleton in podocyte FP. Importantly, the actin filaments are connected to the underlying GBM at focal contacts via an α3β1 integrin complex (3,4). The bends of the actin filament arches appear to be connected directly to the microtubules of the major processes (own unpublished results). FP are anchored to the GBM via α3β1 integrin (5) and dystroglycans (6,7). Neighboring FP are connected by a cell-cell junction, the glomerular SD, which represents the main size selective filter barrier in the kidney (8–10). The SD is thought to be a modified adherens junction (11) that is composed of a growing number of proteins, including nephrin (12–14), P-cadherin, CD2AP (15–18), ZO-1 (19), FAT (20), podocin (16,21), and possibly Neph1 (see reference 22 and below). In addition to the contractile proteins described above, we have reported the association of synaptopodin with the actin filaments in FP (23). Synaptopodin is the first member of a novel class of proline-rich proteins (24) and, like α-actinin-4, interacts with the tight junction protein MAGI-1 (25) that is also expressed in podocytes (26).