title: Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein.
abstract: Synapses are highly specialized sites of cell-cell contact involved in signal transfer. The molecular mechanisms modulating the assembly and stability of synapses are unknown. We previously reported the identification of a 90 kDa synapse-associated protein, SAP90, that is localized at the presynaptic termini of inhibitory GABAergic synapses. SAP90 is a mosaic protein composed of three 90 amino acid residue repeats, an SH3 domain and a region homologous to guanylate kinases. SAP90 shares domain specific homology with a family of proteins involved in the assembly and possibly stability of sites of cell contact. These include the product of the lethal(1) discs-large-1 (dlgA) tumor suppressor gene and the zonula occludens proteins ZO-1, ZO-2. The further characterization of cDNA clones encoding components of synaptic junctions has lead to the identification of a 97 kDa protein, called SAP97, that exhibits a strong overall sequence similarity to SAP90. The present study was undertaken to determine the spatial distribution of SAP97, and to reveal further clues to the possible roles of these proteins in synapses. Light and immunoelectron microscopic analysis of the rat hippocampal formation revealed that SAP97 is localized in the presynaptic nerve termini of excitatory synapses. In other brain regions, SAP97 is found in and along bundles of unmyelinated axons. SAP97 is not restricted to the CNS, but is also present at the basal lateral membrane between a variety of epithelial cells. In cultured T84 cells, it is restricted to the cytoplasmic surface of the plasma membranes between adjacent cells, but not at the edges of cells lacking cell-cell contact suggesting a role for SAP97 in cell adhesion. These data suggest that members of the SAP90/SAP97 subfamily may be involved in the site specific assembly, stability or functions of membrane specialization at sites of cell-cell contact.
authors.affiliation: Center for Molecular Neurobiology, University of Hamburg, Germany.
authors.forename: B M
authors.initials: BM
authors.lastname: Müller
authors.forename: U
authors.initials: U
authors.lastname: Kistner
authors.forename: R W
authors.initials: RW
authors.lastname: Veh
authors.forename: C
authors.initials: C
authors.lastname: Cases-Langhoff
authors.forename: B
authors.initials: B
authors.lastname: Becker
authors.forename: E D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: C C
authors.initials: CC
authors.lastname: Garner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000737:chemistry; D001483:Base Sequence; D001923:Brain Chemistry; D002531:Cerebellum / Q000378:metabolism / Q000648:ultrastructure; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics; D017344:Genes, Insect; D016147:Genes, Tumor Suppressor; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D017403:In Situ Hybridization; D007301:Insect Hormones / Q000737:chemistry*; D007365:Intercellular Junctions / Q000737:chemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D009928:Organ Specificity; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000074407:SAP90-PSD95 Associated Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013569:Synapses / Q000737:chemistry*; D025521:Tumor Suppressor Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; C501119:Dlg1 protein, rat; D029721:Drosophila Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000074407:SAP90-PSD95 Associated Proteins; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila