European Journal of Experimental Biology Open Access

NEK3-mediated serine 105 phosphorylation of SNAP29 modulates its membrane association and SNARE fusion dependent processes

International Conference on Glycobiology

September 21-22, 2017 HOUSTON, TX, USA

Debora Rapaport, Boris Fichtman, Eli Sprecher and Mia Horowitz

Tel Aviv University, Israel Bar-Ilan University, Israel Tel Aviv Sourasky Medical Center, Israel

Scientific Tracks Abstracts: Eur J Exp Bio

Abstract:

Intracellular membrane fusion depends on the presence of specific mediators, the vesicle (v-) and the target (t-) SNAREs (Soluble N-ethylmaleimide-sensitive factor, NSF, attachment protein SNAP receptors), which interaction brings apposing membranes to proximity and initiates their fusion. The v-SNAREs consist of vesicleassociated membrane proteins (VAMP) whereas t-SNAREs include a syntaxin and a synaptosomal-associated protein (SNAP). SNAP29 is involved in multiple fusion events during intracellular transport and therefore affects structure of organelles such as the Golgi apparatus and the focal adhesions. Mutations in SNAP29 gene lead to Cerebral Dysgenesis, Neuropathy, Ichthyosis, and palmoplantar Keratoderma (CEDNIK) syndrome. In the present study, we show that NEK3 (NIMA-never in mitosis gene A-related kinase 3)- mediated serine 105 (S105) phosphorylation of SNAP29 directs its membrane association, without which cells present defective focal adhesion formation, impaired Golgi structure and attenuated cellular recycling. Wildtype SNAP29, in contrast to a phosphorylation-defective serine 105 to alanine (S105A) SNAP29 mutant, partially rescued the abnormal morphology of CEDNIK patient-derived fibroblasts. Our results highlight the importance of S105 phosphorylation of SNAP29, mediated by NEK3, for its membrane localization and therefore, for membrane fusion dependent processes. In this seminar, I will characterize the molecular aspects of the rare genetic syndrome denominated CEDNIK and I will discuss the post-translational modification of SNAP29 and its biological significance.

Biography :

Debora Rapaport works on Genetics and Molecular Cell Biology. She works at the lab of Prof. Mia Horowitz which focuses on genetic disorders and their association with intracellular trafficking. The methodologies we utilize in the lab are based on molecular cell biology, RNAi, knockout mice models and confocal microscopy as a tool to identify diverse cellular phenotypes related with intracellular trafficking.