Formins, also known as formin homology (FH) proteins, are involved in a wide range of actin-mediated processes. The Diaphanous-related formin Daam1 (Dishevelled-associated activator of morphogenesis) interacts with the PDZ domain protein Dishevelled, and is required to establish planar cell polarity in Xenopus. Through a yeast two-hybrid screen, I characterized a PDZ-mediated interaction between the C-terminus of Daam1 and the PDZ domains 456 of GRIP1. In dissociated rat hippocampal cultures, Daam1 expression was seen throughout the soma and dendrites in a punctate pattern. Furthermore, co-staining with a synaptic marker suggests that Daam1 could be associated with post-synaptic specializations. Dendritic spines are enriched with actin filaments, and based on the subcellular localization of Daam1 and the evidence that formins are involved in regulating actin polymerization, I hypothesized that Daam1 might play a role in dendritic spine morphology. In order to investigate the functional roles for Daam1, viral vectors were developed using the Semliki-Forest defective viral vector to over-express the full-length Daam1 protein and a Daam1 lacking the PDZ-binding motif. The over-expression of the full-length Daam1 in organotypic hippocampal slices showed a punctate distribution throughout the dendritic shaft, with the occasional appearance in spines, resulting in an overall increase in dendritic spine length. This suggests that formins, such as Daam1, could potentially regulate spine morphology.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.98789 |
| Date | January 2006 |
| Creators | Salomon, Steven. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biology.) |
| Rights | © Steven Salomon, 2006 |
| Relation | alephsysno: 002482545, proquestno: AAIMR24790, Theses scanned by UMI/ProQuest. |
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