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PMID:7748555

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Citation

DiFiglia, M, Sapp, E, Chase, K, Schwarz, C, Meloni, A, Young, C, Martin, E, Vonsattel, JP, Carraway, R and Reeves, SA (1995) Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14:1075-81

Abstract

The gene defective in Huntington's disease encodes a protein, huntingtin, with unknown function. Antisera generated against three separate regions of huntingtin identified a single high molecular weight protein of approximately 320 kDa on immunoblots of human neuroblastoma extracts. The same protein species was detected in human and rat cortex synaptosomes and in sucrose density gradients of vesicle-enriched fractions, where huntingtin immunoreactivity overlapped with the distribution of vesicle membrane proteins (SV2, transferrin receptor, and synaptophysin). Immunohistochemistry in human and rat brain revealed widespread cytoplasmic labeling of huntingtin within neurons, particularly cell bodies and dendrites, rather than the more selective pattern of axon terminal labeling characteristic of many vesicle-associated proteins. At the ultrastructural level, immunoreactivity in cortical neurons was detected in the matrix of the cytoplasm and around the membranes of the vesicles. The ubiquitous cytoplasmic distribution of huntingtin in neurons and its association with vesicles suggest that huntingtin may have a role in vesicle trafficking.

Links

PubMed

Keywords

Animals; Antibody Specificity; Brain/ultrastructure; Brain Chemistry; Cell Fractionation; Centrifugation, Density Gradient; Cytoplasm/chemistry; Dendrites/chemistry; Humans; Huntington Disease/metabolism; Immune Sera/immunology; Immunochemistry; Mutation; Nerve Tissue Proteins/analysis; Nerve Tissue Proteins/genetics; Neuroblastoma; Neurons/ultrastructure; Nuclear Proteins/analysis; Nuclear Proteins/genetics; Rats; Tumor Cells, Cultured

Significance

Annotations

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

HUMAN:HD

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

located_in

GO:0030659: cytoplasmic vesicle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

is_active_in

GO:0099523: presynaptic cytosol

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

is_active_in

GO:0099524: postsynaptic cytosol

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

is_active_in

GO:0099523: presynaptic cytosol

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

is_active_in

GO:0099523: presynaptic cytosol

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0030659: cytoplasmic vesicle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0099524: postsynaptic cytosol

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0000061)
  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0099523: presynaptic cytosol

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0000061)
  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0099523: presynaptic cytosol

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0000061)
  • part_of:(UBERON:0000956)

Seeded From UniProt

complete

HUMAN:HD

part_of

GO:0099523: presynaptic cytosol

ECO:0000279: western blot evidence used in manual assertion

C

  • part_of:(UBERON:0000061)
  • part_of:(UBERON:0000956)

Seeded From UniProt

complete


See also

References

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