(Postponed - Date to be announced) Senior Seminar Series - Claire Martin

The MCB Graduate Student Council and The Fifth will be hosting Claire Martin as part of our upcoming Senior Seminar Series on Thursday, October 26^th from 4:30-5:30PM. For more information, see the attached poster and abstract below:

Nck1/2 phosphotyrosine adaptors dictate podocyte cytoarchitecture and adhesion by modulation of integrin ß1 signaling

Abstract: Kidney podocytes contribute to blood filtration selectivity through a network of actin-based projections termed foot processes. The ability of these structures to withstand hemodynamic strain and maintain filtration barrier integrity is proposed to be tied to their unique and flexible cytoarchitecture.  However, the molecular mechanisms that regulate such mechanotransduction, including how podocytes remain attached to the underlying glomerular basement membrane, are not well understood. We have previously established that the Nck1/2 family of actin adaptor proteins is essential in podocytes for both the induction and maintenance of foot processes. We now demonstrate that Nck signaling regulates the major podocyte adhesion protein integrin ß1. Mouse podocyte cell lines lacking Nck1/2 show striking defects in f-actin patterning, cell adhesion, spreading and migration. In addition, focal adhesions in these cells are significantly larger and more numerous and centrally localized than their wildtype counterparts. Molecular analysis reveals enhanced activation and surface expression of integrin ß1 as well as overexpression of alpha-actinin 4, an f-actin bundling protein that is also a prominent component of mature focal adhesions. These results are consistent with defective focal adhesion turnover in the absence of Nck, leading to disruption of adhesion. Accordingly, mice lacking both Nck1 and Nck2 expression in podocytes show evidence of podocyte detachment, in addition to defects in integrin ß1 and alpha-actinin 4 expression. Moreover, intermediate defects are observed in cells and animals with loss of Nck1 or Nck2, leading to increased susceptibility to acute injury and podocyte loss in vivo. We conclude that a threshold of Nck proteins is required to regulate podocyte actin remodeling and dynamic focal adhesion turnover in response to strain and that this occurs via modulation of integrin ß1 signaling.

Be sure to come out for some great scientific discussions over drinks and free appetizers!

Your MCB GSC