Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Dynamics of mutated GFAP … - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Dynamics of mutated GFAP aggregates revealed by real-time imaging of an astrocyte model of Alexander disease.

Artikel i vetenskaplig tidskrift
Författare Cyril Mignot
Cécile Delarasse
Séverine Escaich
Bruno Della Gaspera
Eric Noé
Emma Colucci-Guyon
Charles Babinet
Milos Pekny
Patrick Vicart
Odile Boespflug-Tanguy
André Dautigny
Diana Rodriguez
Danielle Pham-Dinh
Publicerad i Experimental cell research
Volym 313
Nummer/häfte 13
Sidor 2766-79
ISSN 0014-4827
Publiceringsår 2007
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 2766-79
Språk en
Länkar dx.doi.org/10.1016/j.yexcr.2007.04....
Ämnesord Alexander Disease, genetics, metabolism, pathology, Animals, Apoptosis, Astrocytes, chemistry, metabolism, ultrastructure, Disease Models, Animal, Glial Fibrillary Acidic Protein, analysis, genetics, metabolism, Green Fluorescent Proteins, analysis, genetics, Heat-Shock Proteins, analysis, metabolism, Mice, Mice, Knockout, Mutation, Ubiquitin, metabolism
Ämneskategorier Fysiologi, Cellbiologi

Sammanfattning

Alexander disease (AxD) is a rare neurodegenerative disorder characterized by large cytoplasmic aggregates in astrocytes and myelin abnormalities and caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), the main intermediate filament protein in astrocytes. We tested the effects of three mutations (R236H, R76H and L232P) associated with AxD in cells transiently expressing mutated GFAP fused to green fluorescent protein (GFP). Mutated GFAP-GFP expressed in astrocytes formed networks or aggregates similar to those found in the brains of patients with the disease. Time-lapse recordings of living astrocytes showed that aggregates of mutated GFAP-GFP may either disappear, associated with cell survival, or coalesce in a huge juxtanuclear structure associated with cell death. Immunolabeling of fixed cells suggested that this gathering of aggregates forms an aggresome-like structure. Proteasome inhibition and immunoprecipitation assays revealed mutated GFAP-GFP ubiquitination, suggesting a role of the ubiquitin-proteasome system in the disaggregation process. In astrocytes from wild-type-, GFAP-, and vimentin-deficient mice, mutated GFAP-GFP aggregated or formed a network, depending on qualitative and quantitative interactions with normal intermediate filament partners. Particularly, vimentin displayed an anti-aggregation effect on mutated GFAP. Our data indicate a dynamic and reversible aggregation of mutated GFAP, suggesting that therapeutic approaches may be possible.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?