Common protein complex may be involved
The loss of functions of Spatacsin and Spastizin in SPG11 and SPG15 mutations respectively cause complicated HSP. Both proteins show similarities in their expression, location and association that could account for similarities in the complicated HSP caused by each.
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.
SOURCE: Mol Cell Neurosci. 2011 Apr 27. [Epub ahead of print]
Cellular distribution and subcellular localization of spatacsin and spastizin, two proteins involved in hereditary spastic paraplegia.
Murmu RP, Martin E, Rastetter A, Esteves T, Muriel MP, El Hachimi KH, Denora PS, Dauphin A, Fernandez JC, Duyckaerts C, Brice A, Darios F, Stevanin G.
INSERM, U975, Paris, France; 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, Paris, France; CNRS, UMR 7225, Paris, France.