Irinka Castanon
PROJECT
Anthrax Toxin Receptor/Tumor Endothelial Marker 8 (TEM8) was the first anthrax receptor identified. The related capillary morphogenesis gene 2 (CMG2) protein was subsequently shown to have anthrax toxin receptor functions. TEM8 and CMG2 are type I transmembrane proteins with single membrane spanning domains. Their most distinctive feature is an extracellular region that binds directly to the anthrax toxin and is related to the von Willerbrand factor A domain. TEM8 and CMG2 proteins are conserved between diverse species, including mouse, rat and zebrafish, suggesting that they fulfill an important physiological function. There is evidence suggesting that these proteins are adhesion molecules involved in angiogenesis. However, their precise function is unknown.
To unravel the endogenous role of the Anthrax Toxin Receptors, we analyze their function during fish development. We found 6 zebrafish anthrax toxin receptor homologs to the human TEM8 and CMG2. Morpholino (MO)-mediated gene knockdown of each of these genes showed a variety of phenotypes including Wnt/beta-catenin-dependent dorso-vetral patterning defects as well as defects during angiogenesis.
From all zebrafish Anthrax Toxin Receptors, we have focused on zAntr2a, the closest homolog of the human CMG2. zAntr2a is polarized at the plasma membrane of gastrulating cells. In dividing cells, zAntr2a localizes to the contractile ring and , after cytokinesis, persists at the cytoplasmic bridge. In antr2a deficient embryos, the convergence and extension (CE) movements required for axis formation are impaired. Antr2a genetically interacts with components of the PCP pathway and the CE phenotype can be rescued by the overexpression of RhoA.
EDUCATION/ACADEMIC BACKGROUND
I did my phD at the Memorial Sloan-Kettering in New York working on muscle development in Drosophila under the supervsion of Dr. Mary Baylies. Then, I moved to the MPI in Dresden, Germany where I worked on fish in the lab of C.P. Heisenberg. There, I studied cell biological processes in a developmental context. In Gonzalez lab, I continue bridging cell biology and developmental biology by stdying the role of the Anthrax Toxin Receptors during zebrafish development.