Investigating Tom1 as a Candidate Regulator of Ptch1

Abstract

Sonic hedgehog (Shh) is a signaling molecule that is involved in patterning the embryo and regulates adult stem cell homeostasis. Patched1 (Ptch1) is the receptor for Shh and upon binding to Shh is endocytosed, allowing downstream signaling to occur. Ptch1 is critical to the cellular response to Shh because it is both a negative regulator of the Shh signaling pathway and a transcriptional target of the pathway. Therefore, the regulation of Ptch1 levels will directly affect the ability of cells to respond to Shh. Understanding this process requires the characterization of novel Ptch1-interacting proteins that regulate Ptch1 levels in the cell. This thesis investigated a role for the adapter protein Tom1 as a putative Ptch1-interacting protein involved in regulating Ptch1 levels through endocytic cycling. It was found that Tom1 overexpression did not regulate the patterning of vertebrate nervous system, but did play a role the sub-cellular localization of Ptch1.