title: Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies.
abstract: Intact synaptic homeostasis is a fundamental prerequisite for a healthy brain. Thus, it is not surprising that altered synaptic morphology and function are involved in the molecular pathogenesis of so-called synaptopathies including autism, schizophrenia (SCZ) and Alzheimer's disease (AD). Intriguingly, various recent studies revealed a crucial role of postsynaptic ProSAP/Shank scaffold proteins in all of the aforementioned disorders. Considering these findings, we follow the hypothesis that ProSAP/Shank proteins are key regulators of synaptic development and plasticity with clear-cut isoform-specific roles. We thus propose a model where ProSAP/Shank proteins are in the center of a postsynaptic signaling pathway that is disrupted in several neuropsychiatric disorders.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Grabrucker
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
authors.forename: Michael
authors.initials: M
authors.lastname: Schoen
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000378:metabolism / Q000473:pathology; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics / Q000378:metabolism; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D009473:Neuronal Plasticity; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human; C492357:SHANK3 protein, human