2007
DOI: 10.1523/jneurosci.4226-07.2007
|View full text |Cite
|
Sign up to set email alerts
|

The G59S Mutation in p150gluedCauses Dysfunction of Dynactin in Mice

Abstract: The G59S missense mutation at the conserved microtubule-binding domain of p150 glued , a major component of dynein/dynactin complex, has been linked to an autosomal dominant form of motor neuron disease (MND). To study how this mutation affects the function of the dynein/dynactin complex and contributes to motor neuron degeneration, we generated p150 glued G59S knock-in mice. We found that the G59S mutation destabilizes p150 glued and disrupts the function of dynein/dynactin complex, resulting in early embryon… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

4
82
0

Year Published

2008
2008
2020
2020

Publication Types

Select...
5
3

Relationship

0
8

Authors

Journals

citations
Cited by 106 publications
(86 citation statements)
references
References 36 publications
4
82
0
Order By: Relevance
“…7b,e). Together with the observation that the G59S mutation destabilizes p150 glued and disrupts dynactin function (Lai et al, 2007), our findings indicate that the normal functions of dynactin p150…”
Section: Of Mutant Dynactin P150supporting
confidence: 71%
See 2 more Smart Citations
“…7b,e). Together with the observation that the G59S mutation destabilizes p150 glued and disrupts dynactin function (Lai et al, 2007), our findings indicate that the normal functions of dynactin p150…”
Section: Of Mutant Dynactin P150supporting
confidence: 71%
“…Glued (Dctn1 m/m ) in mice is embryonically lethal as observed in Dctn1 Ϫ/Ϫ (Lai et al, 2007), our results indicating that mutant dynactin p150…”
Section: Discussionsupporting
confidence: 58%
See 1 more Smart Citation
“…Furthermore, it is noted that patients carrying the H46R mutation, which does not interact with dynein and is not prone to form inclusions in this study, survive 6 -8 times longer than patients carrying the A4V mutation that shows strong interaction with dynein and high aggregation capacity (30 -36). Analysis of various dynein-dynactin mutant mice have revealed that different dynein-dynactin functions, such as long distance ret-rograde transport and dynein-dependent degradative pathways can be affected independently of each other (59,60). Although blockage of the role of dynein in inclusion formation might be beneficial, dynein is also essential to reduce toxicity by clearing away inclusions once inclusions form.…”
Section: Discussionmentioning
confidence: 99%
“…A similar animal model to study the pathogenic mechanism of the G59S mutation in vivo is represented by p150Glued G59S knock-in mice. These mice develop a late-onset, slowly progressive MN disease characterized by abnormal accumulation of NFs and synaptic vesicle proteins at the NMJs, loss of MNs, and gait abnormalities (Lai et al, 2007). LaMonte and coworkers (2002) engineered a targeted disruption of the dynein-dynactin complex in MNs of transgenic mice by overexpression of a subunit of dynactin (dynamitin, p50) that causes the disassembly of the whole complex.…”
Section: Cytoskeletal Protein Mutations: Dynactin Neurofilaments Pementioning
confidence: 99%