title: The hidden life of NAD+-consuming ectoenzymes in the endocrine system.
abstract: Ectoenzymes are a family of cell surface molecules whose catalytic domain lies in the extracellular region. A subset of this family, nucleotide-metabolizing ectoenzymes, are key components in the regulation of the extracellular balance between nucleotides (e.g. NAD(+) or ATP) and nucleosides (e.g. adenosine). Their substrates and products are signalling molecules that act by binding to specific receptors, triggering signals that regulate a variety of functions, ranging from the migration of immune cells, to synaptic transmission in the brain, to hormone/receptor interactions in the glands. Almost two decades of accumulated data indicate that these regulatory processes significantly affect the endocrine system, a tightly controlled information signal complex with clear evidence of fine regulation. Functional models discussed in this review include insulin secretion, bone modelling and the association between hormones and behaviour. The emerging pattern is one of a system operating as a scale-free network that hinges around hubs of key molecules, such as NAD(+) or ATP. The underlying natural link between nucleotides, ectoenzymes and the endocrine system is far from being clearly demonstrated. However, the body of evidence supporting the existence of such connection is growing exponentially. This review will try to read the available evidence in a hypothesis-oriented perspective, starting from the description of NAD(+) and of ecto- and endoenzymes involved in its metabolism.
authors.affiliation: Laboratory of Immunogenetics and CeRMS, Department of Genetics, Biology and Biochemistry, University of Torino School of Medicine, Turin, Italy. fabio.malavasi@unito.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Gianluca
authors.initials: G
authors.lastname: Zaccarello
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Horenstein
authors.forename: Antonella
authors.initials: A
authors.lastname: Chillemi
authors.forename: Valentina
authors.initials: V
authors.lastname: Audrito
authors.forename: Sara
authors.initials: S
authors.lastname: Serra
authors.forename: Marina
authors.initials: M
authors.lastname: Gandione
authors.forename: Andrea
authors.initials: A
authors.lastname: Zitella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tizzani
mesh_terms: D000818:Animals; D004703:Endocrine System / Q000201:enzymology*; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*
chemical_list: D004798:Enzymes; D009243:NAD