Characterization of mesencephalic astrocyte-derived neurotrophic factor of Suberites domuncula
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Abstract
Sponges have been considered the earliest branching metazoan taxon, and therefore, are important in the reconstruction of early metazoan evolution. Besides, sponges lack a conventional nervous system, which provides an enticing opportunity to explore the evolutionary ancient role of neurotrophic factors and thus the understanding of specific Metazoan genetic toolkits and molecular signaling pathways. The mesencephalic astrocyte-derived neurotrophic factor (MANF) together with cerebral dopamine neurotrophic factor composes a family of evolutionarily conserved neurotrophic factors each selectively protects dopaminergic neurons. MANF is generally resident within the endoplasmic reticulum (ER) but can also be secreted. It is widely expressed in neurons and non-neuronal tissues. MANF is involved in the ER stress response and also has pro-survival effects. Here is reported the identification of the MANF homolog from the sponge Suberites domuncula (SDMANF). SDMANF possesses significant sequence similarity with its metazoan homologs. In Suberites, SDMANF is expressed in the vicinity of bacteriocytes and surrounding a eukaryotic sponge endobiont. In human embryonic kidney cells transfected with SDMANF, the protein was identified in the organelle protein fraction and also in the cell culture medium. The intracellular SDMANF level was up-regulated in response to a Golgi/ER transport inhibitor brefeldin A, and the apoptosis inducers cadmium and lipopolysaccharide (LPS). Upon LPS exposition, transfected cells present a reduced caspase 3 activity and enhanced cell viability with no increased expression of BCL-2-associated X (BAX) in comparison with not transfected cells/ wild-type cells. The aforementioned results suggest MANF has roles in cytoprotection with crossing functions on innate immunity and apoptosis pathways that were deeply evolutionary preserved, besides the neurotrophic function, which might have emerged later in metazoan evolution.