Valeria Mastrodonato

First name
Valeria
Last name
Mastrodonato
Year of Study
Thesis Title
The study of Snap29 in mitosis and in CEDNIK pathogenesis
Thesis Abstract
The fusion between a vesicle and a target membrane is a key step of intracellular trafficking mediated by SNARE proteins. Snap29 is a cytosolic SNARE protein, whose specificity and activity is unclear. During the last few years, Snap29 was discovered to be a key regulator of autophagy required for fusion of autophagosomes with lysosomes. During my PhD, I contributed to uncover a novel function of Snap29 in Drosophila, demonstrating that during mitosis Snap29 acts as a kinetochore component and it is required to ensure proper cell division. Indeed, depletion of Snap29 in S2 cells determines defective chromosome segregation, often leading to cell death. In addition, we observed that Snap29 ensures correct tissue development and homeostasis in Drosophila, since its depletion or mutation causes epithelial multilayering and tumor-like tissue alterations. Since mutations affecting autophagy genes are not sufficient per se to induce such disruptions, we hypothesize that these defects might be also due to loss of Snap29 activity during mitosis.
Mutations of SNAP29 human gene cause a rare syndrome called CEDNIK, which leads to severe neurological and dermatological manifestations So far, the most investigated aspects of this syndrome are dermatological alterations, likely caused by the impairment of SNAP29 activity during membrane trafficking. To study uncharacterized CEDNIK traits, we took advantage of a zebrafish snap29 mutant and we found that, beside known CEDNIK symptoms, they display trigeminal nerve formation and axonal branching defects, suggesting the requirement of Snap29 for correct nervous system development. Overall, our findings demonstrate that Snap29 is a key regulator of cell division and shed light on uncharacterized aspects of CEDNIK syndrome, suggesting a pivotal role of Snap29 in nervous system development.
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