title: The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels.
abstract: Rer1 is a sorting receptor in the early secretory pathway that controls the assembly and the cell surface transport of selected multimeric membrane protein complexes. Mice with a Purkinje cell (PC) specific deletion of Rer1 showed normal polarization and differentiation of PCs and normal development of the cerebellum. However, PC-specific loss of Rer1 led to age-dependent motor deficits in beam walk, ladder climbing and gait. Analysis of brain sections revealed a specific degeneration of PCs in the anterior cerebellar lobe in old animals. Electrophysiological recordings demonstrated severe deficits in spontaneous action potential generation. Measurements of resurgent currents indicated decreased surface densities of voltage-gated sodium channels (Nav), but not changes in individual channels. Analysis of mice with a whole brain Rer1-deletion demonstrated a strong down-regulation of Nav1.6 and 1.1 in the absence of Rer1, whereas protein levels of the related Cav2.1 and of Kv3.3 and 7.2 channels were not affected. The data suggest that Rer1 controls the assembly and transport of Nav1.1 and 1.6, the principal sodium channels responsible for recurrent firing, in PCs.
authors.affiliation: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, 07743 Jena, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Valkova
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Liebmann
authors.affiliation: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, 07743 Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Krämer
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.affiliation: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, 07743 Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaether
mesh_terms: D000200:Action Potentials; D033942:Adaptor Proteins, Vesicular Transport; D000375:Aging / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017353:Gene Deletion; D018345:Mice, Knockout; D009043:Motor Activity; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011689:Purkinje Cells / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018160:Receptors, Cytoplasmic and Nuclear; C556092:Rer1 protein, mouse; D061566:Voltage-Gated Sodium Channels