title: The Ca2+ sensor protein swiprosin-1/EFhd2 is present in neurites and involved in kinesin-mediated transport in neurons.
abstract: Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/-/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre- and post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport.
authors.affiliation: Division of Molecular Immunology, Dept. of Internal Medicine III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Pavitra
authors.initials: P
authors.lastname: Purohit
authors.affiliation: IZKF Nachwuchsgruppe III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Francesc
authors.initials: F
authors.lastname: Perez-Branguli
authors.affiliation: IZKF Nachwuchsgruppe III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Iryna
authors.initials: I
authors.lastname: Prots
authors.affiliation: School of Biology, Medical and Biological Sciences Building, University of St. Andrews, North Haugh, St Andrews, Fife, United Kingdom.
authors.forename: Eva
authors.initials: E
authors.lastname: Borger
authors.affiliation: School of Biology, Medical and Biological Sciences Building, University of St. Andrews, North Haugh, St Andrews, Fife, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: Gunn-Moore
authors.affiliation: Department of Psychiatry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Welzel
authors.affiliation: Department of Psychiatry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Loy
authors.affiliation: Department of Psychiatry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Wenzel
authors.affiliation: Department of Psychiatry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Teja W
authors.initials: TW
authors.lastname: Grömer
authors.affiliation: Division of Molecular Immunology, Dept. of Internal Medicine III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brachs
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany, and Leibniz Institute for Age Research, Jena, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Holzer
authors.affiliation: Institute for Neuropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Buslei
authors.affiliation: Division of Molecular Immunology, Dept. of Internal Medicine III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Fritsch
authors.affiliation: IZKF Nachwuchsgruppe III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Regensburger
authors.affiliation: Fritz Lipmann Institute, Molecular Motors Lab, Jena, Germany.
authors.forename: Konrad J
authors.initials: KJ
authors.lastname: Böhm
authors.affiliation: IZKF Nachwuchsgruppe III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Winner
authors.affiliation: Division of Molecular Immunology, Dept. of Internal Medicine III, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mielenz
mesh_terms: D000818:Animals; D001370:Axonal Transport; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D016547:Kinesins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism*; D021381:Protein Transport; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C530752:EFHD2 protein, mouse; D016547:Kinesins