PhD Exit Seminar – Jordan Silver (Tepass lab)

PhD Exit Seminar

Thursday May 12^th, 2:10 pm – Ramsay Wright Building, Rm. 432

Jordan Silver (Tepass lab) 

“Yurt and Cysts Link Adherens Junction Stability to Actomyosin Remodeling in Drosophila Embryogenesis“

Abstract

The integrity of epithelial cells relies on the stability of adherens junctions (AJs) during development. This dissertation focused on how remodeling of the actomyosin cytoskeleton can stabilize AJs.

The FERM domain protein Yurt acts as a basolateral polarity regulator without any known interaction partners. I showed that Yurt genetically interacts with myosin II and DE-cadherin (DEcad) to support epithelial integrity in the Drosophila embryo. I found that a pool of Yurt localizes to AJs and physically interacts with myosin II and members of the cadherin-catenin complex. Loss of Yurt leads to fragmentation of AJs and disruption of myosin II throughout the ectoderm. In dorsal closure, I demonstrated that Yurt is essential for the recruitment of DEcad to the leading edge (LE) -amnioserosa interface and assembly of the LE multicellular myosin II cable. Yurt appears to support the LE cable through the organization of apical Crumbs and aPKC. In wound healing, we showed that Yurt can be recruited de novo to the site of myosin II cable assembly. I propose a model where an apical pool of Yurt acts to link the cadherin-catenin complex and the actomyosin cytoskeleton to stabilize AJs.

Next, I characterized a novel RhoGEF, Cysts (previously CG10188), that is essential for epithelial polarity in the Drosophila embryo. RhoGEFs can regulate actomyosin effectors through targeting of small Rho GTPases. I found that Cysts is required for epithelial cell polarity. Depletion of Cysts leads to a progressive reduction in myosin II in the early embryonic ectoderm, followed by a disruption of AJs and apicobasal polarity, ultimately leading to cellular apoptosis. Structure-function analysis demonstrated that the RhoGEF domain and the C-terminal region of Cysts are essential for function. We showed that the C-terminal region of Cysts facilitates recruitment to apical junctions, whereas genetic and biochemical experiments suggested that Cysts predominantly activates Rho1 rather than Cdc42 or Rac. I propose a model whereby Cysts acts through Rho1 to maintain a critical level of myosin II at AJs in support of junctional and epithelial integrity.

Ramsay Wright is a wheelchair accessible building.