title: Lipocalin-type prostaglandin D2 synthase protein regulates glial cell migration and morphology through myristoylated alanine-rich C-kinase substrate: prostaglandin D2-independent effects.
abstract: Prostaglandin D synthase (PGDS) is responsible for the conversion of PGH(2) to PGD(2). Two distinct types of PGDS have been identified: hematopoietic-type PGDS (H-PGDS) and lipocalin-type PGDS (L-PGDS). L-PGDS acts as both a PGD(2)-synthesizing enzyme and as an extracellular transporter of various lipophilic small molecules. Although L-PGDS is one of the most abundant proteins in the cerebrospinal fluid, little is known about the function of L-PGDS in the central nervous system (CNS). To better understand the role of L-PGDS in the CNS, effects of L-PGDS on the migration and morphology of glial cells were investigated. The L-PGDS protein accelerated the migration of cultured glial cells. Expression of the L-pgds gene was detected in glial cells and neurons. L-PGDS protein also induced morphological changes in glia similar to the characteristic phenotypic changes in reactive gliosis. L-PGDS-induced cell migration was associated with augmented formation of actin filaments and focal adhesion, which was accompanied by activation of AKT, RhoA, and JNK pathways. L-PGDS protein injected into the mouse brain promoted migration and accumulation of astrocytes in vivo. Furthermore, the cell migration-promoting effect of L-PGDS on glial cells was independent of the PGD(2) products. The L-PGDS protein interacted with myristoylated alanine-rich protein kinase C substrate (MARCKS) to promote cell migration. These results demonstrate the critical role of L-PGDS as a secreted lipocalin in the regulation of glial cell migration and morphology. The results also indicate that L-PGDS may participate in reactive gliosis in an autocrine or paracrine manner, and may have pathological implications in neuroinflammatory diseases.
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, CMRI, Kyungpook National University School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Shinrye
authors.initials: S
authors.lastname: Lee
authors.forename: Eunha
authors.initials: E
authors.lastname: Jang
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D041681:NIH 3T3 Cells; D009457:Neuroglia / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D054834:Lipocalins; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2