title: Glutaminases in brain: Multiple isoforms for many purposes.
abstract: Glutaminase is expressed in most mammalian tissues and cancer cells, but recent studies are now revealing a considerably degree of complexity in its pattern of expression and functional regulation. Novel transcript variants of the mammalian glutaminase Gls2 gene have been recently found and characterized in brain. Co-expression of different isoforms in the same cell type would allow cells to fine-tune their Gln/Glu levels under a wide range of metabolic states. Moreover, the discovery of protein interacting partners and novel subcellular localizations, for example nucleocytoplasmic in neurons and astrocytes, strongly suggest non-neurotransmission roles for Gls2 isoforms associated with transcriptional regulation and cellular differentiation. Of note, Gls isoforms have been considered as an important trophic factor for neuronal differentiation and postnatal development of brain regions. On the other hand, glutaminases are taking center stage in tumor biology as new therapeutic targets to inhibit metabolic reprogramming of cancer cells. Interestingly, glutaminase isoenzymes play seemingly opposing roles in cancer cell growth and proliferation; this issue will be also succinctly discussed with special emphasis on brain tumors.
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Canceromics Lab. Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Campos-Sandoval
authors.affiliation: Proteomics Lab, Central Facility Core, Universidad de Málaga, 29071 Málaga, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martín-Rufián
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Canceromics Lab. Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cardona
authors.affiliation: Proteomics Lab, Central Facility Core, Universidad de Málaga, 29071 Málaga, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lobo
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Canceromics Lab. Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Peñalver
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Canceromics Lab. Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. Electronic address: marquez@uma.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Márquez
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics; D005972:Glutaminase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000473:pathology
chemical_list: D007527:Isoenzymes; D005972:Glutaminase
keywords: Brain; Cancer; Glioma; Glutamate; Glutaminase isoforms; Glutamine