Afadin is localized at cell–cell contact sites in mesangial cells and regulates migratory polarity

Abstract

In kidney glomeruli, mesangial cells provide structural support to counteract for expansile forces caused by pressure gradients and to regulate the blood flow. Glomerular injury results in proliferation and aberrant migration of mesangial cells, which is the pathological characteristic of mesangial proliferative glomerulonephritis. To date, molecular changes that occur in mesangial cells during glomerular injury and their association with the pathogenesis of glomerulonephritis remain largely unclear. During the search for proteins regulating the morphology of mesangial cells, we found that afadin, a multi-domain F-actin-binding protein, and β-catenin are expressed in cell–cell contact sites of cultured mesangial cells and mesangial cells in vivo. Afadin forms a protein complex with β-catenin in glomeruli and in cultured mesangial cells. Protein expression of afadin at mesangial intercellular junctions was dramatically decreased in mesangial proliferative nephritis in rats and in patients with glomerulonephritis. RNA interference-mediated depletion of afadin in cultured mesangial cells did not affect proliferation rate but resulted in delayed directional cell migration. Furthermore, reorientation of the Golgi complex at the leading edges of migrating cells in wound-healing assay was disturbed in afadin-depleted cells, suggesting the role of aberrant migratory polarity in the pathogenesis of proliferative glomerulonephritis. These data shed light on glomerulonephritis-associated changes in cell–cell adhesion between mesangial cells, which might be related to migratory polarity.

NGL‐3‐induced presynaptic differentiation of hippocampal neurons in an afadin‐dependent, nectin‐1‐independent manner

“…; Tsurumi et al . ), but it is not known whether afadin forms a complex with β‐catenin or γ‐catenin in the brain. In the last set of experiments, we examined whether β‐catenin and/or γ‐catenin was co‐immunoprecipitated with afadin from the lysate of the light membrane fraction of mouse brain.…”

“…; Tsurumi et al . ). Therefore, one possible mechanism for the role of afadin in the presynaptic differentiation is that afadin regulates the NGL‐3‐LAR system through the α‐catenin–β‐catenin complex.…”

“…This b-catenin regulates the accumulation of the undocked SVs, presumably the SVs in the reserved pool (Bamji et al 2003). Afadin binds to b-catenin indirectly through a-catenin or directly Tsurumi et al 2016). Therefore, one possible mechanism for the role of afadin in the presynaptic differentiation is that afadin regulates the NGL-3-LAR system through the a-catenin-b-catenin complex.…”

“…cateninTsurumi et al 2016), but it is not known whether afadin forms a complex with b-catenin or c-catenin in the brain. In the last set of experiments, we examined whether b-catenin Localizations of l-afadin and s-afadin at mossy fiber synapses.…”

Listeria monocytogenesInlP interacts with afadin and facilitates basement membrane crossing

“…Two unbiased screening methods to identify potential placental binding partners, a yeast two-hybrid screen using a placental cDNA library and mass spectrometric identification of human proteins pulled down by InlP from placental extracts, converged on afadin as a significant candidate binding partner. Afadin is not found on the cell surface, but instead is primarily associated with the cytoplasmic face of cell-cell junctions containing nectin (41, 53). Therefore, it seems likely that InlP is most helpful in breaching that third barrier and accessing the fetal stroma.…”