Presenter: Lyle McPherson
Mentor: Ken Prehoda
Poster: 23
Major: Biochemistry
Cell polarity regulates important functions for metazoan cells, including epithelial, neuronal and stem cells. However, little is known about the molecular mechanisms that allow cells to establish cell polarity. aPKC, the kinase of the evolutionarily conserved Par complex, polarizes cellular proteins. In these polarized cells, protein polarization genetically downstream of aPKC maintains tissue integrity and establishes cell identity. For multiple aPKC substrates, phosphorylation induces protein polarization by displacing substrates from aPKCcontaining membrane domains. Despite the clear role of aPKC in establishing cell polarity the molecular mechanism by which aPKC’s kinase activity polarizes its substrates remains unclear. We characterized the polarization mechanism of Numb, an aPKC substrate, using cell biology and biochemistry. We identified lipidbinding sites within Numb that mediate its recruitment to the cellular cortex by binding to negatively charged phospholipids. Additionally, we found that specific amino acids within these sites are phosphorylated by aPKC to inhibit lipid binding. Our findings suggest one mechanism for aPKCmediated cell polarity where aPKC polarizes Numb by phosphorylating it to inhibit cortical association thereby resulting in its polarization. We are currently investigating other domains of Numb containing aPKC phosphorylation sites to further our understanding of the molecular mechanisms behind this process. The mechanism of Numb’s polarization by aPKC illustrates to us a way that a kinase can induce cell polarity by destabilizing a protein’s membrane association in specific regions of the cell.