title: SNAP-25, a Known Presynaptic Protein with Emerging Postsynaptic Functions.
abstract: A hallmark of synaptic specializations is their dependence on highly organized complexes of proteins that interact with each other. The loss or modification of key synaptic proteins directly affects the properties of such networks, ultimately impacting synaptic function. SNAP-25 is a component of the SNARE complex, which is central to synaptic vesicle exocytosis, and, by directly interacting with different calcium channels subunits, it negatively modulates neuronal voltage-gated calcium channels, thus regulating intracellular calcium dynamics. The SNAP-25 gene has been associated with distinct brain diseases, including Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia and bipolar disorder, indicating that the protein may act as a shared biological substrate among different "synaptopathies". The mechanisms by which alterations in SNAP-25 may concur to these psychiatric diseases are still undefined, although alterations in neurotransmitter release have been indicated as potential causative processes. This review summarizes recent work showing that SNAP-25 not only controls exo/endocytic processes at the presynaptic terminal, but also regulates postsynaptic receptor trafficking, spine morphogenesis, and plasticity, thus opening the possibility that SNAP-25 defects may contribute to psychiatric diseases by impacting not only presynaptic but also postsynaptic functions.
authors.affiliation: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano Milan, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Antonucci
authors.affiliation: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di MilanoMilan, Italy; Istituto di Neuroscienze, Centro Nazionale RicercheMilan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Corradini
authors.affiliation: Humanitas Clinical and Research Center, IRCCS Rozzano Rozzano, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fossati
authors.affiliation: Humanitas Clinical and Research Center, IRCCS Rozzano Rozzano, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Tomasoni
authors.affiliation: Istituto di Neuroscienze, Centro Nazionale RicercheMilan, Italy; Humanitas Clinical and Research Center, IRCCS RozzanoRozzano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Menna
authors.affiliation: Istituto di Neuroscienze, Centro Nazionale RicercheMilan, Italy; Humanitas Clinical and Research Center, IRCCS RozzanoRozzano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
keywords: SNAP-25; brain diseases; postsynaptic role; presynaptic role; synaptopathies