title: Cellular distribution and subcellular localization of spatacsin and spastizin, two proteins involved in hereditary spastic paraplegia.
abstract: Truncating mutations in the SPG11 and SPG15 genes cause complicated spastic paraplegia, severe neurological conditions due to loss of the functions of spatacsin and spastizin, respectively. We developed specific polyclonal anti-spatacsin (SPG11) and anti-spastizin (SPG15) antisera, which we then used to explore the intracellular and tissue localizations of these proteins. We observed expression of both proteins in human and rat central nervous system, which was particularly strong in cortical and spinal motor neurons as well as in retina. Both proteins were also expressed ubiquitously and strongly in embryos. In cultured cells, these two proteins had similar diffuse punctate, cytoplasmic and sometimes nuclear (spastizin) distributions. They partially co-localized with multiple organelles, particularly with protein-trafficking vesicles, endoplasmic reticulum and microtubules. Spastizin was also found at the mitochondria surface. This first study of the endogenous expression of spatacsin and spastizin shows similarities in their expression patterns that could account for their overlapping clinical phenotypes and involvement in a common protein complex.
authors.affiliation: INSERM, U975, Université Pierre et Marie Curie-Paris 6, UMR_S975, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CR-icm), GHU Pitié-Salpêtrière, CNRS, Paris, France.
authors.forename: Reena Prity
authors.initials: RP
authors.lastname: Murmu
authors.forename: Elodie
authors.initials: E
authors.lastname: Martin
authors.forename: Agnès
authors.initials: A
authors.lastname: Rastetter
authors.forename: Typhaine
authors.initials: T
authors.lastname: Esteves
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Muriel
authors.forename: Khalid Hamid
authors.initials: KH
authors.lastname: El Hachimi
authors.forename: Paola Silvia
authors.initials: PS
authors.lastname: Denora
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dauphin
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Fernandez
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Frédéric
authors.initials: F
authors.lastname: Darios
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011506:Proteins; C520412:SPG11 protein, human; C528699:ZFYVE26 protein, human