The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons

Chameau, Pascal; Inta, Dragoš; Vitalis, Tania; Monyer, Hannah; Wadman, Wytse J.; Hooft, Johannes A. van

doi:10.1073/pnas.0810764106

Cited by 107 publications

(131 citation statements)

References 40 publications

(56 reference statements)

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“…Alternatively, the NR2 fragment may be anchored to specific regions by an uncharacterized mechanism. It has been reported that the Reelin NR2 fragment negatively regulates dendritic maturation in an ApoER2/VLDLR-independent manner in the cerebral cortex (48). How the localization of the NR2 fragment is regulated and whether it plays a role in the hippocampus are important questions to be answered.…”

Section: Discussionmentioning

confidence: 99%

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Cleavage within Reelin Repeat 3 Regulates the Duration and Range of the Signaling Activity of Reelin Protein

Koie¹,

Okumura²,

Hisanaga

et al. 2014

Journal of Biological Chemistry

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Background:The physiological role of Reelin proteolysis is largely uncharacterized. Results: An "uncleavable" Reelin mutant remains active for a long time, and the cleaved Reelin fragment localizes differently than full-length Reelin. Conclusion: Extracellular and intracellular Reelin cleavage is required for halting downstream signaling and transport of the cleaved product. Significance: Inhibition of Reelin cleavage will be beneficial for treating neuropsychiatric diseases.

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Section: Discussionmentioning

confidence: 99%

“…It has also been suggested that the NR2 fragment and fulllength Reelin may function independently (48). Therefore, it is important to characterize the localization of full-length Reelin and its fragments to understand their roles.…”

Section: Endosomal Reelin N-t Cleavage Is Required For Halting the Damentioning

confidence: 99%

Cleavage within Reelin Repeat 3 Regulates the Duration and Range of the Signaling Activity of Reelin Protein

Koie¹,

Okumura²,

Hisanaga

et al. 2014

Journal of Biological Chemistry

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“…Interestingly, tissue plasminogen activator, shown to be induced by and involved in removal of Aβ aggregates (Tucker et al, 2000), cleaves Reelin at its C-terminal end (Krstic et al, 2012b) and by that modulate its binding to ApoER2 (Nakano et al, 2007). However, the biological significance of the proteolytic processing of Reelin might be more complex (Jossin et al, 2007, Chameau et al, 2009, and likely involves more downstream effects than only reducing binding of Reelin to its receptors, as previously proposed (Kohno et al, 2009). …”

Section: Dysfunctional Reelin Signaling and Its Role In Ad Etiologymentioning

confidence: 97%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD. AbstractAlzheimer`s disease (AD) is one of the largest unmet medical needs of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles (NFTs), the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiology characteristic of late-onset AD.3

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“…The latter may, however, not be entirely dependent on Apoer2 and Vldlr (Chameau et al 2009) and may also involve interactions with APP (Hoe et al 2009). Reelin signaling also regulates dendritic spine morphology (Costa et al 2001;Niu et al 2008;Pujadas et al 2010), which likely involves regulation of actin dynamics and the participation of n-cofilin (Chai et al 2009;Rust et al 2010).…”

Section: Regulation Of Dendritic Spines Glutamatergic Neurotransmissmentioning

confidence: 99%

Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

Holtzman

Herz²,

2012

Cold Spring Harbor Perspectives in Medicine

673

602

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The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons

Cited by 107 publications

References 40 publications

Cleavage within Reelin Repeat 3 Regulates the Duration and Range of the Signaling Activity of Reelin Protein

Cleavage within Reelin Repeat 3 Regulates the Duration and Range of the Signaling Activity of Reelin Protein

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

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