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PMID:23483716

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Citation

'Sudarov, A, Gooden, F, Tseng, D, Gan, WB and Ross, ME (2013) Lis1 controls dynamics of neuronal filopodia and spines to impact synaptogenesis and social behaviour. EMBO Mol Med '

Abstract

LIS1 (PAFAH1B1) mutation can impair neuronal migration, causing lissencephaly in humans. LIS1 loss is associated with dynein protein motor dysfunction, and disrupts the actin cytoskeleton through disregulated RhoGTPases. Recently, LIS1 was implicated as an important protein-network interaction node with high-risk autism spectrum disorder genes expressed in the synapse. How LIS1 might participate in this disorder has not been investigated. We examined the role of LIS1 in synaptogenesis of post-migrational neurons and social behaviour in mice. Two-photon imaging of actin-rich dendritic filopodia and spines in vivo showed significant reductions in elimination and turnover rates of dendritic protrusions of layer V pyramidal neurons in adolescent Lis1(+/-) mice. Lis1(+/-) filopodia on immature hippocampal neurons in vitro exhibited reduced density, length and RhoA dependent impaired dynamics compared to Lis1(+/+) . Moreover, Lis1(+/-) adolescent mice exhibited deficits in social interaction. Lis1 inactivation restricted to the postnatal hippocampus resulted in similar deficits in dendritic protrusion density and social interactions. Thus, LIS1 plays prominently in dendritic filopodia dynamics and spine turnover implicating reduced dendritic spine plasticity as contributing to developmental autistic-like behaviour.

Links

PubMed Online version:10.1002/emmm.201202106

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LIS1

GO:0061003: positive regulation of dendritic spine morphogenesis

ECO:0000315:

P

Figure 4

complete
CACAO 6967

MOUSE:LIS1

GO:0044419: interspecies interaction between organisms

ECO:0000315:

P

Figure 6 - In the experiment it showed that Lis1+/− mutant mice exhibit asocial behaviour in a 3-chamber social interaction test. Whenever the mice had the wt gene they interacted normally but with the Lis1+/- they were much more antisocial; showing that Lis1 is involved with interspecies interaction.

complete
CACAO 6970

MOUSE:LIS1

involved_in

GO:0061003: positive regulation of dendritic spine morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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