Astn2, A Novel Member of the Astrotactin Gene Family, Regulates the Trafficking of ASTN1 during Glial-Guided Neuronal Migration

Wilson, Perrin M.; Fryer, Robert H.; Yin, Fei; Hatten, Mary E.

doi:10.1523/jneurosci.0032-10.2010

Cited by 153 publications

(180 citation statements)

References 47 publications

Supporting

Mentioning

172

Contrasting

Order By: Relevance

“…Treatment with dynasore delayed the nuclear movement in the locomoting neurons (Fig. 6A,B), as previously reported (Wilson et al, 2010), and also decreased both the ratio of cells with a cytoplasmic dilation and the ratio of length to width of the nuclei ( Fig. 6C-E; supplementary material Movie 4).…”

Section: Inhibition Of Endocytic Trafficking Disturbs Dilation Formatsupporting

confidence: 87%

Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons

et al. 2014

View full text Add to dashboard Cite

Neuronal migration is crucial for development of the mammalian-specific six-layered cerebral cortex. Migrating neurons are known to exhibit distinct features; they form a cytoplasmic dilation, a structure specific to migrating neurons, at the proximal region of the leading process, followed by nuclear elongation and forward movement. However, the molecular mechanisms of dilation formation and nuclear elongation remain unclear. Using ex vivo chemical inhibitor experiments, we show here that rottlerin, which is widely used as a specific inhibitor for PKCδ, suppresses the formation of a cytoplasmic dilation and nuclear elongation in cortical migrating neurons. Although our previous study showed that cortical neuronal migration depends on Jnk, another downstream target of rottlerin, Jnk inhibition disturbs only the nuclear elongation and forward movement, but not the dilation formation. We found that an unconventional cyclin-dependent kinase, Cdk5, is a novel downstream target of rottlerin, and that pharmacological or knockdown-mediated inhibition of Cdk5 suppresses both the dilation formation and nuclear elongation. We also show that Cdk5 inhibition perturbs endocytic trafficking as well as microtubule organization, both of which have been shown to be required for dilation formation. Furthermore, knockdown of Dcx, a Cdk5 substrate involved in microtubule organization and membrane trafficking, or p27 kip1 , another Cdk5 substrate involved in actin and microtubule organization, disturbs the dilation formation and nuclear elongation. These data suggest that Cdk5 and its substrates, Dcx and p27 kip1 , characterize migrating neuronspecific features, cytoplasmic dilation formation and nuclear elongation in the mouse cerebral cortex, possibly through the regulation of microtubule organization and an endocytic pathway.

show abstract

Section: Inhibition Of Endocytic Trafficking Disturbs Dilation Formatsupporting

confidence: 87%

Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons

et al. 2014

View full text Add to dashboard Cite

show abstract

“…[20][21][22][23] Alternatively, the cognitive impairment may be related to the fact that the deletion also includes part of the ASTN2 gene that codes for astrotactin 2, a brain protein possibly involved in neuronal migration. 11 A recent large study revealed that heterozygous copy number variations affecting the 3′-terminal part of ASTN2 or both ASTN2 and TRIM32 are significantly enriched in males with neurodevelopmental and neurobehavioral disorders. 13 In this study, the patient with cognitive impairment has a homozygous deletion of ASTN2, whereas the other patient, heterozygous for the ASTN2 deletion, does not present any intellectual disability.…”

Section: Discussionmentioning

confidence: 99%

Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing

Nectoux¹,

Cid²,

Baulande³

et al. 2014

Eur J Hum Genet

View full text Add to dashboard Cite

Defects in TRIM32 were reported in limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and in Bardet-Biedl syndrome. Few cases have been described to date in LGMD2H/STM, but this gene is not systematically analysed because of the absence of specific signs and difficulties in protein analysis. By using high-throughput variants screening techniques, we identified variants in TRIM32 in two patients presenting nonspecific LGMD. We report the first case of total inactivation by homozygous deletion of the entire TRIM32 gene. Of interest, the deletion removes part of the ASTN2 gene, a large gene in which TRIM32 is nested. Despite the total TRIM32 gene inactivation, the patient does not present a more severe phenotype. However, he developed a mild progressive cognitive impairment that may be related to the loss of function of ASTN2 because association between ASTN2 heterozygous deletions and neurobehavioral disorders was previously reported. Regarding genomic characteristics at breakpoint of the deleted regions of TRIM32, we found a high density of repeated elements, suggesting a possible hotspot. These observations illustrate the importance of high-throughput technologies for identifying molecular defects in LGMD, confirm that total loss of function of TRIM32 is not associated with a specific phenotype and that TRIM32/ASTN2 inactivation could be associated with cognitive impairment.

show abstract

“…[46][47][48][49][50][51] Our analysis adds profilin1 as another novel regulator of CGN-glial cell interaction. In fact, we found reduced levels of vinculin and Mena in junctures of profilin1-deficient CGN and control glial cells.…”

Section: Profilin1 Is Important For Glial Cell Binding and Radial Migmentioning

confidence: 99%

Role of the actin-binding protein profilin1 in radial migration and glial cell adhesion of granule neurons in the cerebellum

Rust

Kullmann

Witke

2012

Cell Adhesion & Migration

View full text Add to dashboard Cite

Astn2, A Novel Member of the Astrotactin Gene Family, Regulates the Trafficking of ASTN1 during Glial-Guided Neuronal Migration

Cited by 153 publications

References 47 publications

Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons

Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons

Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing

Role of the actin-binding protein profilin1 in radial migration and glial cell adhesion of granule neurons in the cerebellum

Contact Info

Product

Resources

About