HUNTINGTIN IS A CYTOPLASMIC PROTEIN ASSOCIATED WITH VESICLES IN HUMAN AND RAT-BRAIN NEURONS

被引:605
作者
DIFIGLIA, M
SAPP, E
CHASE, K
SCHWARZ, C
MELONI, A
YOUNG, C
MARTIN, E
VONSATTEL, JP
CARRAWAY, R
REEVES, SA
BOYCE, FM
ARONIN, N
机构
[1] HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114
[2] HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114
[3] UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA 01655
[4] UNIV MASSACHUSETTS,MED CTR,DEPT PHYSIOL,WORCESTER,MA 01655
[5] UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655
关键词
D O I
10.1016/0896-6273(95)90346-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 similar to 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.
引用
收藏
页码:1075 / 1081
页数:7
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