RESEARCH: Spastin

[Guest guest]

Identification of nuclear localisation sequences in

spastin (SPG4) using a novel Tetra-GFP reporter

system.

Beetz C, Brodhun M, Moutzouris K, Kiehntopf M, Berndt

A, Lehnert D, Deufel T, Bastmeyer M, Schickel J.

Institut fur Pathologie, Klinikum der

Friedrich-Schiller Universitat Jena, Ziegelmuhlenweg

1, 07740 Jena, Germany.

Mutations in the human spastin gene (SPG4) cause the

most prevalent form of autosomal dominant hereditary

spastic paraplegia (HSP), a neurodegenerative disorder

characterised by progressive weakness and spasticity

of the lower limbs. We address the question of

intracellular localisation of spastin. Using

polyclonal antibodies against N-terminal spastin

sequences, we find that the native protein is

localised in both the perinuclear cytoplasm and the

nucleus. To identify structural motifs within the

protein that can explain entry into the nucleus, we

developed a reporter system to test nuclear

localisation sequence (NLS)-functionality based on

four in-frame fused copies of green fluorescent

protein. Using this novel tool we demonstrate that

spastin carries two NLSs located in exons 1 and 6.

Both are independently functional in mediating nuclear

entry.

SOURCE: Biochem Biophys Res Commun. 2004 Jun

11;318(4):1079-84.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5147984 & dopt=Abstract