title: Expression of LPP3 in Bergmann glia is required for proper cerebellar sphingosine-1-phosphate metabolism/signaling and development.
abstract: Bioactive lipids serve as intracellular and extracellular mediators in cell signaling in normal and pathological conditions. Here we describe that an important regulator of some of these lipids, the lipid phosphate phosphatase-3 (LPP3), is abundantly expressed in specific plasma membrane domains of Bergmann glia (BG), a specialized type of astrocyte with key roles in cerebellum development and physiology. Mice selectively lacking expression of LPP3/Ppap2b in the nervous system are viable and fertile but exhibit defects in postnatal cerebellum development and modifications in the cytoarchitecture and arrangement of BG with a mild non-progressive motor coordination defect. Lipid and gene profiling studies in combination with pharmacological treatments suggest that most of these effects are associated with alterations in sphingosine-1-phosphate (S1P) metabolism and signaling. Altogether our data indicate that LPP3 participates in several aspects of neuron-glia communication required for proper cerebellum development.
authors.affiliation: Instituto de Fisiología Celular, División de Neurociencias, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Juárez
authors.forename: Sara
authors.initials: S
authors.lastname: Morales-Lázaro
authors.forename: Roberto
authors.initials: R
authors.lastname: Sánchez-Sánchez
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.forename: Hilda
authors.initials: H
authors.lastname: Lomelí
authors.forename: Iván
authors.initials: I
authors.lastname: Velasco
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Diana
authors.initials: D
authors.lastname: Escalante-Alcalde
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002452:Cell Count; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D009924:Organ Culture Techniques; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism*; D045442:Rotarod Performance Test; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D010711:Phosphatidate Phosphatase; C479566:Plpp3 protein, mouse; D013110:Sphingosine