Neuronal position in the developing brain is regulated by mouse disabled-1

Howell, Brian W.; Hawkes, Richard; Soriano, Philippe; Cooper, Jonathan A.

doi:10.1038/39607

Cited by 664 publications

(522 citation statements)

References 22 publications

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“…It has been well established that reelin signaling is linearly transmitted through apoER2, VLDLR, and the intracellular adaptor protein Dab1, resulting in activation of Src family tyrosine kinases (Howell et al, 1997;D'Arcangelo et al, 1999;Arnaud et al, 2003). We have shown previously that bath perfusion of reelin increases the magnitude of tetanusinduced LTP of field potentials in CA1 (Weeber et al, 2002), presumably as a result of Src activation and enhanced NMDAR function to facilitate LTP induction.…”

Section: Reelin Enhances Pairing-induced Ltp Of Synaptic Responsesmentioning

confidence: 99%

“…Transduction of reelin signaling occurs through interaction of disabled-1 (Dab1) with the intracellular NPxY motif of these receptors, resulting in tyrosine phosphorylation of Dab1, activation of the SFKs (Src family nonreceptor tyrosine kinases), and an ensuing signaling cascade that leads to proper neuronal migration (Howell et al, 1997(Howell et al, , 1999aTrommsdorff et al, 1998;Arnaud et al, 2003;Bock and Herz, 2003). Considering the fact that reelin is also abundantly expressed by interneurons, and all of the downstream signaling components exist in the postnatal hippocampus (Alcantara et al, 1998;Pesold et al, 1998;Abraham and Meyer, 2003;Zhao et al, 2004), it is intriguing to know whether reelinmediated signaling plays a physiological role in adult brain function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Reelin-Induced Enhancement of NMDA and AMPA Receptor Activity in the Adult Hippocampus

Qiu¹,

Zhao²,

Korwek³

et al. 2006

J. Neurosci.

159

158

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The developmental lamination of the hippocampus and other cortical structures requires a signaling cascade initiated by reelin and its receptors, apoER2 (apolipoprotein E receptor 2) and VLDLR (very-low-density lipoprotein receptor). However, the functional significance of continued reelin expression in the postnatal brain remains poorly understood. Here, we show that reelin application to adult mice hippocampal slices leads to enhanced glutamatergic transmission mediated by NMDA receptors (NMDARs) and AMPA receptors (AMPARs) through distinct mechanisms. Application of recombinant reelin enhanced NMDAR-mediated currents through postsynaptic mechanisms, as revealed by the variance-mean analysis of synaptic NMDAR currents, assessment of spontaneous miniature events, and the levels of NMDAR subunits at synaptic surface. In comparison, nonstationary fluctuation analysis of miniature AMPAR currents and quantification of synaptic surface proteins revealed that reelin-induced enhancement of AMPAR responses was mediated by increased AMPAR numbers. Reelin enhancement of synaptic NMDAR currents was abolished when receptor-associated protein (RAP) or the Src inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1) was bath applied and was abrogated by includingPP1 in the recording electrodes. In comparison, including RAP or an inactive PP1 analog PP3 in the recording electrode was without effect. Interestingly, the increased AMPAR response after reelin application was not blocked by PP1 but was blocked by the phosphoinositide-3Ј kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride]. Furthermore, reelin-induced, PI3K-dependent AMPAR surface insertion was also observed in cultured hippocampal neurons. Together, these results reveal a differential functional coupling of reelin signaling with NMDAR and AMPAR function and define a novel mechanism for controlling synaptic strength and plasticity in the adult hippocampus.

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Section: Reelin Enhances Pairing-induced Ltp Of Synaptic Responsesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Reelin-Induced Enhancement of NMDA and AMPA Receptor Activity in the Adult Hippocampus

Qiu¹,

Zhao²,

Korwek³

et al. 2006

J. Neurosci.

159

158

View full text Add to dashboard Cite

show abstract

“…Reelin is a large extracellular glycoprotein secreted by Cajal-Retzius cells and mediating proper positioning of neurons during development through the activation of the apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR, (D'Arcangelo et al, 1995Hiesberger et al, 1999;Howell et al, 1997;Tommsdorff et al, 1999). Transduction of the signal involves the interaction of the adapter protein Dab1 with the intracellular NPxY motiv of these receptors, resulting in tyrosine phosphorylation of Dab1, activation of Src family of non-receptor tyrosine kinases, and triggering a downstream cytosolic kinase cascade beginning with the activation of phosphatidylinositol-3-kinase (PI3K) and ending with the inhibition of glycogen synthase kinase 3β (GSK3β; for recent review, see Herz and Cheng, 2006).…”

Section: Introductionmentioning

confidence: 99%

Age-related accumulation of Reelin in amyloid-like deposits

Knuesel

Nyffeler

Mormède

et al. 2009

Neurobiology of Aging

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Age-related accumulation of Reelin in amyloid-like deposits Abstract Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits. These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Abeta species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD. ABSTRACTAccumulating evidence suggest that alterations in Reelin-mediated signalling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits.These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Aβ species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD.3

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“…Dab1, the brain-speci®c homolog, was ®rst identi®ed as a Src kinase binding protein (Howell et al, 1997a). In Dab1-de®cient mice, brain neuronal cells are disorganized and fail to form discrete layers, a phenotype similar to the reeler mutant mice, in which the ECM protein reelin is mutated (D'Arcangelo et al, 1997;Howell et al, 1997b;Sheldon et al, 1997). Mice that are de®cient in both the apolipoprotein E receptor 2 (apoER2) and VLDL receptor have an indistinguishable phenotype from reeler and Dab1 defective mice (Trommsdor et al, 1999).…”

Section: Introductionmentioning

confidence: 99%