Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons.
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.
DiFiglia
M
M
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Sapp
E
E
Chase
K
K
Schwarz
C
C
Meloni
A
A
Young
C
C
Martin
E
E
Vonsattel
J P
JP
Carraway
R
R
Reeves
S A
SA
D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000648:ultrastructure*; D001923:Brain Chemistry; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D003593:Cytoplasm / Q000737:chemistry*; D003712:Dendrites / Q000737:chemistry; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism*; D007106:Immune Sera / Q000276:immunology; D007120:Immunochemistry; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D009447:Neuroblastoma; D009474:Neurons / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D051381:Rats; D014407:Tumor Cells, Cultured
C086055:HTT protein, human; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D007106:Immune Sera; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins