The Slit family (Slit1-3) of secreted glycoproteins and their cognate Roundabout family (Robo1-4) of transmembrane receptors provide important repulsive signals to guide cell migration during development and postnatal life. The dynamic regulation of Slit/Robo signaling is poorly understood in vertebrates. In this study, we identified a novel role for endocytosis in regulating Slit2 /Robo1 expression. Using heterologous expression systems, Slit2 was found be endocytosed in a Robo1-dependent manner and subsequently degraded in the lysosome, while Robo1 was found to be primarily recycled. An AP-2 consensus binding site, which mediates clathrin-dependent endocytosis, was identified in the Robo1 cytoplasmic tail and found to be required for Slit2 down-regulation and Slit2-induced endocytosis of Robo1. Preliminary data suggests that Slit2-induced endocytosis of Robo1 may be required for downstream signaling. These findings have important implications for how Slit/Robo signaling may be dynamically regulated during cell migration.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33577 |
| Date | 27 November 2012 |
| Creators | Wang, Heng Rui |
| Contributors | Fish, Jason |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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