Mast syndrome is an inherited genetic disorder with severe neurological symptoms. A frameshift mutation leading to the loss of maspardin protein was identified as the major cause of mast syndrome. However, the normal cellular function of maspardin is not well known. By utilizing a mouse model of mast syndrome the present study aims to elucidate the potential role of maspardin in selected cellular signaling pathways in hippocampus. Results show that maspardin is expressed in multiple organs. Co-localization studies performed in the hippocampal tissue of control mice identified maspardin forms a complex with the early endosomal Ras-related GTPase, Rab5, but not with Rab7, which is mainly located in late endosomes. In the hippocampus of maspardin knock-out mice (Mas mice), brain derived neurotrophic factor (BDNF) levels were downregulated. However, protein expression levels of nerve growth factor (NGF) were not altered. Furthermore, pro-inflammatory molecules such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were not altered and phosphorylation of β-catenin, low-density lipoprotein receptor-related protein 6 (LRP6), and extracellular signal regulated kinase 1/2 (ERK1/2) remained unchanged. Behavioral analysis showed Mas mice did not exhibit elevated anxiety. These results indicate that maspardin is associated with early endosomal processing and potentially regulates BDNF signaling.

 

Keywords: maspardin, hippocampus, endosome, BDNF, Rab