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PMID:19619244

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Citation

Matsushita-Ishiodori, Y, Yamanaka, K, Hashimoto, H, Esaki, M and Ogura, T (2009) Conserved aromatic and basic amino acid residues in the pore region of Caenorhabditis elegans spastin play critical roles in microtubule severing. Genes Cells 14:925-40

Abstract

Mutations of human spastin, an AAA (ATPases associated with diverse cellular activity) family protein, cause an autosomal dominant form of hereditary spastic paraplegia, which is characterized by weakness, spasticity and loss of the vibratory sense in the lower limbs. Recently, it has been reported that spastin displays microtubule-severing activity. We also previously reported that Caenorhabditis elegans spastin homologue SPAS-1 displays microtubule severing. However, the detailed molecular mechanism of microtubule severing remains unknown. Here, we describe that SPAS-1 forms a stable hexamer in a concentration-dependent manner and that ATPase activity of SPAS-1 is greatly stimulated by microtubules. Furthermore, MTBD (microtubule-binding domain) of SPAS-1 is essential for binding to microtubules. Taken these results together, we propose that MTBD of SPAS-1 plays a critical role in enrichment of SPAS-1 to microtubules, where SPAS-1 is concentrated and able to form a stable hexamer, subsequently its ATPase activity is stimulated. On the other hand, our mutational analyses revealed that the conserved aromatic and basic amino acid residues in the pore region are important for microtubule severing. We also detected the direct interaction of the extremely acidic C-terminal polypeptide of tubulin with SPAS-1. Consequently, we propose that the central pore residues are important for the recognition of substrates.

Links

PubMed Online version:10.1111/j.1365-2443.2009.01320.x

Keywords

Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Amino Acids, Aromatic/chemistry; Amino Acids, Basic/chemistry; Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Humans; Microtubules/metabolism; Microtubules/ultrastructure; Models, Molecular; Mutation; Spastic Paraplegia, Hereditary/metabolism; Surface Plasmon Resonance; Tubulin/chemistry; Tubulin/genetics; Tubulin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:SPAST

enables

GO:0008017: microtubule binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:SPAST

enables

GO:0008568: microtubule-severing ATPase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:SPAST

enables

GO:0016887: ATP hydrolysis activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:SPAST

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8MNV0

F

Seeded From UniProt

complete

CAEEL:SPAST

involved_in

GO:0051013: microtubule severing

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:SPAST

part_of

GO:0032991: protein-containing complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8MNV0

C

Seeded From UniProt

complete


See also

References

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