EurekaMag
+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Tabanidae
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Huntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion at the plasma membrane


Huntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion at the plasma membrane



Disease Models and Mechanisms 7(12): 1335-1340



ISSN/ISBN: 1754-8403

PMID: 25368120

DOI: 10.1242/dmm.017368

Huntingtin is a large membrane-associated scaffolding protein that associates with endocytic and exocytic vesicles and modulates their trafficking along cytoskeletal tracks. Although the progression of Huntington's disease is linked to toxic accumulation of mutant huntingtin protein, loss of wild-type huntingtin function might also contribute to neuronal cell death, but its precise function is not well understood. Therefore, we investigated the molecular role of huntingtin in exocytosis and observed that huntingtin knockdown in HeLa cells causes a delay in endoplasmic reticulum (ER)-to-Golgi transport and a reduction in the number of cargo vesicles leaving the trans-Golgi network. In addition, we found that huntingtin is required for secretory vesicle fusion at the plasma membrane. Similar defects in the early exocytic pathway were observed in primary fibroblasts from homozygous Htt(140Q/140Q) knock-in mice, which have the expansion inserted into the mouse huntingtin gene so lack wild-type huntingtin expression. Interestingly, heterozygous fibroblasts from a Huntington's disease patient with a 180Q expansion displayed no obvious defects in the early secretory pathway. Thus, our results highlight the requirement for wild-type huntingtin at distinct steps along the secretory pathway.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053616453

Download citation: RISBibTeXText

Related references

The identification of the SNARE complex required for the fusion of VLDL-transport vesicle with hepatic cis-Golgi. Biochemical Journal 429(2): 391-401, 2010

COPII proteins are required for Golgi fusion but not for endoplasmic reticulum budding of the pre-chylomicron transport vesicle. Journal of Cell Science 116(Part 2): 415-427, 2003

Copii proteins are required for Golgi fusion but not for endoplasmic reticulum budding of the pre-chylomicron transport vesicle. Journal of Cell Science 116(2): 415-427, 2003

Cytosolic ARFs are required for vesicle formation but not for cell-free intra-Golgi transport: evidence for coated vesicle-independent transport. Molecular Biology of the Cell 5(2): 237-252, 1994

Cholesterol is required for efficient endoplasmic reticulum-to-Golgi transport of secretory membrane proteins. Molecular Biology of the Cell 17(4): 1593-1605, 2006

Myosin VI and its binding partner optineurin are involved in secretory vesicle fusion at the plasma membrane. Molecular Biology of the Cell 22(1): 54-65, 2011

The membrane transport factor TAP/p115 cycles between the Golgi and earlier secretory compartments and contains distinct domains required for its localization and function. Journal of Cell Biology 143(2): 319-331, 1998

Bos1p, an integral membrane protein of the endoplasmic reticulum to golgi transport vesicles, is required for their fusion competence. Cell 73(4): 735-745, 1993

Transport of biosynthetic sphingolipids from Golgi to plasma membrane in HT29 cells: involvement of different carrier vesicle populations. European Journal of Cell Biology 63(2): 172-181, 1994

Evidence that electrostatic interactions between vesicle-associated membrane protein 2 and acidic phospholipids may modulate the fusion of transport vesicles with the plasma membrane. Molecular Biology of the Cell 20(23): 4910-4919, 2009

VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane. Plos Genetics 13(4): E1006698, 2017

Effect of ethanol on intracellular vesicular transport from Golgi to the apical cell membrane: Role of phosphatidylinositol 3-kinase and phospholipase A2 in Golgi transport vesicles association and fusion with the apical membrane. Alcoholism Clinical and Experimental Research 22(1): 167-175, 1998

Kinesin and dynamin are required for post-Golgi transport of a plasma-membrane protein. Nature Cell Biology 2(2): 125-127, 2000

Identification and characterization of glucose transport proteins in plasma membrane- and Golgi vesicle-enriched fractions prepared from lactating rat mammary gland. Biochemical Journal 272(1): 99-105, 1990

Exocytic transport vesicles generated in vitro from the trans-Golgi network carry secretory and plasma membrane proteins. Proceedings of the National Academy of Sciences of the United States of America 87(19): 7717-7721, 1990