solimena group
Anna Ivanova
THE ROLE OF ICA512 FOR THE DYNAMICS OF SG EXOCYTOSIS
The general aim of my project is to investigate further the role of ICA512. Specifically, I am interested in testing whether ICA512 regulates the exocytosis of a specific subset of SGs and to elucidate the molecular mechanism of this process. Recent studies, in particular, indicate newly formed SGs of neuroendocrine cells are preferentially released. As part of my project I want therefore to investigate whether the cleaved fragment of ICA512 differentially affects the exocytosis of younger and older SGs. To distinguish between different subsets of SGs in respect to their age, I will employ a novel approach called SNAP tagging. This method may also provide quantitative information about the generation and activity of the ICA512 cleaved cytosolic fragment (ICA512-CCF). Preliminary studies in our laboratory suggest that ICA512-CCF heterodimerizes with the intact cytosolic domain of ICA512 on SGs. Therefore, I am interested in determining how this interaction is regulated and its significance for SG exocytosis. The membrane of SGs includes another protein of unknown function called Phogrin/IA-2β whose cytoplasmic domain is 74% identical to that of ICA512. In my project I will determine whether ICA512 forms heterodimers with Phogrin. Moreover, I want to determine the precise cleavage site within the ICA512 cytoplasmic domain in vivo as well as visualize the occurrence of this cleavage in living cells. Overall, this information would provide further insight into the mechanisms for adjusting the exocytosis and production of insulin SGs to metabolic demands.
Contact details:
anna.ivanova {at}
mailbox.tu-dresden.de
+49 (0)3 51 79 63 66 02