Analysis of pin1 expression and function during zebrafish development reveals a dynamic regulation

IBARRA, S.; MARGARIT, E.; MIONE, M.; GIRARDINI, J

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

The prolyl isomerase Pin1 plays a key role in the modulationof proline-directed phosphorylation signaling by inducing localconformational changes in phosphorylated protein substrates.Besides being involved in physiological processes, a large body ofevidences has shown that Pin1 may affect pathological conditions.For example, clinical studies have shown that Pin1 is frequentlyoverexpressed in different cancers and in some cases its overexpressioncorrelates with clinical outcome. Also, its deregulation hasbeen related to brain disorders, including Alzheimer?s, Parkinson?sand Huntington?s disease. Despite several evidences on the effectof Pin1 on specific substrates or signaling pathways, there arestill several unanswered questions regarding its biological roleand, particularly, little is known about its regulation. Notably, thecurrent evidences showing that Pin1 expression and activity maybe regulated by different mechanisms were generated only oncultured cells, and there is almost no evidence of its relevance invivo. Considering the dependence of Pin1 on the particular combinationof protein substrates present in a specific cell type andon the activation of signaling pathways able to phosphorylate itsbinding sites, studies in animal models may provide novel insights,useful to understand proline-directed phosphorylation signalingand the consequences of Pin1 deregulation. Using Danio rerio(zebrafish) as a vertebrate model organism, we showed that pin1expression is regulated during embryogenesis to achieve specificmRNA and protein distribution patterns. Moreover, we found thatPin1 overexpression affected specific regions of the developingembryos and we extended the study of Pin1 expression to the adultzebrafish brain. Our results suggest that specific mechanisms areoperated in different cell types to regulate Pin1 function.