Details

Autor(en) / Beteiligte

• Alami, Nael H
• Smith, Rebecca B
• Carrasco, Monica A
• Williams, Luis A
• Winborn, Christina S
• Han, Steve S W
• Kiskinis, Evangelos
• Winborn, Brett
• Freibaum, Brian D
• Kanagaraj, Anderson
• Clare, Alison J
• Badders, Nisha M
• Bilican, Bilada
• Chaum, Edward
• Chandran, Siddharthan
• Shaw, Christopher E
• Eggan, Kevin C
• Maniatis, Tom
• Taylor, J Paul

Titel

Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations

Ist Teil von

• Neuron (Cambridge, Mass.), 2014-02, Vol.81 (3), p.536-543

Ort / Verlag

United States: Elsevier Limited

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The RNA-binding protein TDP-43 regulates RNA metabolism at multiple levels, including transcription, RNA splicing, and mRNA stability. TDP-43 is a major component of the cytoplasmic inclusions characteristic of amyotrophic lateral sclerosis and some types of frontotemporal lobar degeneration. The importance of TDP-43 in disease is underscored by the fact that dominant missense mutations are sufficient to cause disease, although the role of TDP-43 in pathogenesis is unknown. Here we show that TDP-43 forms cytoplasmic mRNP granules that undergo bidirectional, microtubule-dependent transport in neurons in vitro and in vivo and facilitate delivery of target mRNA to distal neuronal compartments. TDP-43 mutations impair this mRNA transport function in vivo and in vitro, including in stem cell-derived motor neurons from ALS patients bearing any one of three different TDP-43 ALS-causing mutations. Thus, TDP-43 mutations that cause ALS lead to partial loss of a novel cytoplasmic function of TDP-43.