title: HSPB3 protein is expressed in motoneurons and induces their survival after lesion-induced degeneration.
abstract: The human small heat shock proteins (HSPBs) form a family of molecular chaperones comprising ten members (HSPB1-HSPB10), whose functions span from protein quality control to cytoskeletal dynamics and cell death control. Mutations in HSPBs can lead to human disease and particularly point mutations in HSPB1 and HSPB8 are known to lead to peripheral neuropathies. Recently, a missense mutation (R7S) in yet another member of this family, HSPB3, was found to cause an axonal motor neuropathy (distal hereditary motor neuropathy type 2C, dHMN2C). Until now, HSPB3 protein localization and function in motoneurons (MNs) have not yet been characterized. Therefore, we studied the endogenous HSPB3 protein distribution in the spinal cords of chicken and mouse embryos and in the postnatal nervous system (central and peripheral) of chicken, mouse and human. We further investigated the impact of wild-type and mutated HSPB3 on MN cell death via overexpressing these genes in ovo in an avian model of MN degeneration, the limb-bud removal. Altogether, our findings represent a first step for a better understanding of the cellular and molecular mechanisms leading to dHMN2C.
authors: Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albertstraße 17, 79104 Freiburg, Germany. Electronic address: veronicalapadula@gmail.com.
authors: Veronica
authors: V
authors: La Padula
authors: Institute of Neuropathology, Neurozentrum, Breisacherstraße 64, 79106 Freiburg, Germany. Electronic address: ori.staszewski@uniklinik-freiburg.de.
authors: Ori
authors: O
authors: Staszewski
authors: Institute of Anatomy and Cell Biology, Department of Neuroanatomy, Albertstraße 17, 79104 Freiburg, Germany.
authors: Sigrun
authors: S
authors: Nestel
authors: Systems Biology of the Cellular Microenvironment Group, Institute of Molecular Medicine and Cell Research, University of Freiburg, Germany; German Cancer Consortium (DKTK), Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: h.busch@dkfz.de.
authors: Hauke
authors: H
authors: Busch
authors: Systems Biology of the Cellular Microenvironment Group, Institute of Molecular Medicine and Cell Research, University of Freiburg, Germany; German Cancer Consortium (DKTK), Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: m.boerries@dkfz-heidelberg.de.
authors: Melanie
authors: M
authors: Boerries
authors: Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albertstraße 17, 79104 Freiburg, Germany; Institute of Anatomy and Cell Biology, Department of Neuroanatomy, Albertstraße 17, 79104 Freiburg, Germany. Electronic address: eleni.roussa@anat.uni-freiburg.de.
authors: Eleni
authors: E
authors: Roussa
authors: Institute of Neuropathology, Neurozentrum, Breisacherstraße 64, 79106 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany. Electronic address: marco.prinz@uniklinik-freiburg.de.
authors: Marco
authors: M
authors: Prinz
authors: Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albertstraße 17, 79104 Freiburg, Germany. Electronic address: kerstin.krieglstein@uniklinik-freiburg.de.
authors: Kerstin
authors: K
authors: Krieglstein
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000235:genetics; D002642:Chick Embryo; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C557249:HSPB3 protein, mouse; D006360:Heat-Shock Proteins
keywords: Charcot-Marie-Tooth disease; Chicken embryo; Distal hereditary motor neuropathy; In ovo electroporation; Lesion-induced cell death; Motoneuron; Small heat shock proteins