title: Unexpected role of lipocalin-type prostaglandin D synthase in brain: regulation of glial cell migration and morphology.
abstract: Lipocalin-type prostaglandin D synthase (L-PGDS) is one of the most abundant proteins in the cerebrospinal fluid. Nevertheless, its role in the central nervous system is far from clear. Here, we present evidence that L-PGDS induces glial cell migration and morphological changes in vitro and in vivo. We also identified myristoylated alanine-rich C-kinase substrate (MARCKS), heat shock proteins and actin as L-PGDS-binding proteins, demonstrating that MARCKS/Akt/Rho/Jnk pathways are involved in the L-PGDS actions in glia. We further show that the cell migration-promoting activity of L-PGDS is independent of PGD 2 production. The results suggest a novel non-enzymatic function of L-PGDS protein in brain inflammation, and may have an impact on glial cell biology and brain pathology related with reactive gliosis. L-PGDS is a potential drug target that can be exploited for therapeutic intervention of glia-driven neuroinflammation and related diseases.
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu, Korea. ksuk@knu.ac.kr
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000201:enzymology; D002465:Cell Movement; D048430:Cell Shape; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*; D054834:Lipocalins / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009457:Neuroglia / Q000201:enzymology / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase