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Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Biochem+Biophys+Rep 2017 ; 11 (ä): 161-73 Nephropedia Template TP
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An evolutionary perspective on the role of mesencephalic astrocyte-derived neurotrophic factor (MANF): At the crossroads of poriferan innate immune and apoptotic pathways #MMPMID28955781
Sereno D; Müller WE; Bausen M; Elkhooly TA; Markl JS; Wiens M
Biochem Biophys Rep 2017[Sep]; 11 (ä): 161-73 PMID28955781show ga
The mesencephalic astrocyte-derived neurotrophic factor (MANF) belongs to a recently discovered family of neurotrophic factors. MANF can be secreted but is generally resident within the endoplasmic reticulum (ER) in neuronal and non-neuronal cells, where it is involved in the ER stress response with pro-survival effects. Here we report the discovery of the MANF homolog SDMANF in the sponge Suberites domuncula. The basal positioning of sponges (phylum Porifera) in the animal tree of life offers a unique vantage point on the early evolution of the metazoan-specific genetic toolkit and molecular pathways. Since sponges lack a conventional nervous system, SDMANF presents an enticing opportunity to investigate the evolutionary ancient role of these neurotrophic factors. SDMANF shares considerable sequence similarity with its metazoan homologs. It also comprises a putative protein binding domain with sequence similarities to the Bcl-2 family of apoptotic regulators. In Suberites, SDMANF is expressed in the vicinity of bacteriocytes, where it co-localizes with the toll-like receptor SDTLR. In transfected human cells, SDMANF was detected in both the organelle protein fraction and the cell culture medium. The intracellular SDMANF protein level was up-regulated in response to both a Golgi/ER transport inhibitor and bacterial lipopolysaccharides (LPS). Upon LPS challenge, transfected cells revealed a decreased caspase-3 activity and increased cell viability with no inducible Bax expression compared to the wild type. These results suggest a deep evolutionary original cytoprotective role of MANF, at the crossroads of innate immune and apoptotic pathways, of which a neurotrophic function might have arisen later in metazoan evolution.