Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories

Uwe Konietzko, Zoë V. Goodger, Michelle Meyer, Bernhard M. Kohli, Jérôme Bosset, Debomoy Lahiri, Roger M. Nitsch

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The β-amyloid precursor protein (APP) plays a major role in Alzheimer's disease. The APP intracellular domain (AICD), together with Fe65 and Tip60, localizes to spherical nuclear AFT complexes, which may represent sites of transcription. Despite a lack of co-localization with several described nuclear compartments, we have identified a close apposition between AFT complexes and splicing speckles, Cajal bodies and PML bodies. Live imaging revealed that AFT complexes were highly mobile within nuclei and following pharmacological inhibition of transcription fused into larger assemblies. We have previously shown that AICD regulates the expression of its own precursor APP. In support of our earlier findings, transfection of APP promoter plasmids as substrates resulted in cytosolic AFT complex formation at labeled APP promoter plasmids. In addition, identification of chromosomal APP or KAI1 gene loci by fluorescence in situ hybridization showed their close association with nuclear AFT complexes. The transcriptional activator Notch intracellular domain (NICD) localized to the same nuclear spots as occupied by AFT complexes suggesting that these nuclear compartments correspond to transcription factories. Fe65 and Tip60 also co-localized with APP in the neurites of primary neurons. Pre-assembled AFT complexes may serve to assist fast nuclear signaling upon endoproteolytic APP cleavage.

Original languageEnglish
Pages (from-to)58-73
Number of pages16
JournalNeurobiology of Aging
Volume31
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Amyloid beta-Protein Precursor
Plasmids
Neurites
Fluorescence In Situ Hybridization
Amyloid
Transfection
Alzheimer Disease
Pharmacology
Neurons
Genes

Keywords

  • AICD
  • Fe65
  • FISH
  • Live cell imaging
  • NICD
  • Nuclear bodies
  • Nuclear signaling
  • Tip60
  • Transcription

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories. / Konietzko, Uwe; Goodger, Zoë V.; Meyer, Michelle; Kohli, Bernhard M.; Bosset, Jérôme; Lahiri, Debomoy; Nitsch, Roger M.

In: Neurobiology of Aging, Vol. 31, No. 1, 01.2010, p. 58-73.

Research output: Contribution to journalArticle

Konietzko, Uwe ; Goodger, Zoë V. ; Meyer, Michelle ; Kohli, Bernhard M. ; Bosset, Jérôme ; Lahiri, Debomoy ; Nitsch, Roger M. / Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories. In: Neurobiology of Aging. 2010 ; Vol. 31, No. 1. pp. 58-73.
@article{689db5cec9c34b8fb6c8f579b4bbc047,
title = "Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories",
abstract = "The β-amyloid precursor protein (APP) plays a major role in Alzheimer's disease. The APP intracellular domain (AICD), together with Fe65 and Tip60, localizes to spherical nuclear AFT complexes, which may represent sites of transcription. Despite a lack of co-localization with several described nuclear compartments, we have identified a close apposition between AFT complexes and splicing speckles, Cajal bodies and PML bodies. Live imaging revealed that AFT complexes were highly mobile within nuclei and following pharmacological inhibition of transcription fused into larger assemblies. We have previously shown that AICD regulates the expression of its own precursor APP. In support of our earlier findings, transfection of APP promoter plasmids as substrates resulted in cytosolic AFT complex formation at labeled APP promoter plasmids. In addition, identification of chromosomal APP or KAI1 gene loci by fluorescence in situ hybridization showed their close association with nuclear AFT complexes. The transcriptional activator Notch intracellular domain (NICD) localized to the same nuclear spots as occupied by AFT complexes suggesting that these nuclear compartments correspond to transcription factories. Fe65 and Tip60 also co-localized with APP in the neurites of primary neurons. Pre-assembled AFT complexes may serve to assist fast nuclear signaling upon endoproteolytic APP cleavage.",
keywords = "AICD, Fe65, FISH, Live cell imaging, NICD, Nuclear bodies, Nuclear signaling, Tip60, Transcription",
author = "Uwe Konietzko and Goodger, {Zo{\"e} V.} and Michelle Meyer and Kohli, {Bernhard M.} and J{\'e}r{\^o}me Bosset and Debomoy Lahiri and Nitsch, {Roger M.}",
year = "2010",
month = "1",
doi = "10.1016/j.neurobiolaging.2008.03.001",
language = "English",
volume = "31",
pages = "58--73",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories

AU - Konietzko, Uwe

AU - Goodger, Zoë V.

AU - Meyer, Michelle

AU - Kohli, Bernhard M.

AU - Bosset, Jérôme

AU - Lahiri, Debomoy

AU - Nitsch, Roger M.

PY - 2010/1

Y1 - 2010/1

N2 - The β-amyloid precursor protein (APP) plays a major role in Alzheimer's disease. The APP intracellular domain (AICD), together with Fe65 and Tip60, localizes to spherical nuclear AFT complexes, which may represent sites of transcription. Despite a lack of co-localization with several described nuclear compartments, we have identified a close apposition between AFT complexes and splicing speckles, Cajal bodies and PML bodies. Live imaging revealed that AFT complexes were highly mobile within nuclei and following pharmacological inhibition of transcription fused into larger assemblies. We have previously shown that AICD regulates the expression of its own precursor APP. In support of our earlier findings, transfection of APP promoter plasmids as substrates resulted in cytosolic AFT complex formation at labeled APP promoter plasmids. In addition, identification of chromosomal APP or KAI1 gene loci by fluorescence in situ hybridization showed their close association with nuclear AFT complexes. The transcriptional activator Notch intracellular domain (NICD) localized to the same nuclear spots as occupied by AFT complexes suggesting that these nuclear compartments correspond to transcription factories. Fe65 and Tip60 also co-localized with APP in the neurites of primary neurons. Pre-assembled AFT complexes may serve to assist fast nuclear signaling upon endoproteolytic APP cleavage.

AB - The β-amyloid precursor protein (APP) plays a major role in Alzheimer's disease. The APP intracellular domain (AICD), together with Fe65 and Tip60, localizes to spherical nuclear AFT complexes, which may represent sites of transcription. Despite a lack of co-localization with several described nuclear compartments, we have identified a close apposition between AFT complexes and splicing speckles, Cajal bodies and PML bodies. Live imaging revealed that AFT complexes were highly mobile within nuclei and following pharmacological inhibition of transcription fused into larger assemblies. We have previously shown that AICD regulates the expression of its own precursor APP. In support of our earlier findings, transfection of APP promoter plasmids as substrates resulted in cytosolic AFT complex formation at labeled APP promoter plasmids. In addition, identification of chromosomal APP or KAI1 gene loci by fluorescence in situ hybridization showed their close association with nuclear AFT complexes. The transcriptional activator Notch intracellular domain (NICD) localized to the same nuclear spots as occupied by AFT complexes suggesting that these nuclear compartments correspond to transcription factories. Fe65 and Tip60 also co-localized with APP in the neurites of primary neurons. Pre-assembled AFT complexes may serve to assist fast nuclear signaling upon endoproteolytic APP cleavage.

KW - AICD

KW - Fe65

KW - FISH

KW - Live cell imaging

KW - NICD

KW - Nuclear bodies

KW - Nuclear signaling

KW - Tip60

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=70449535896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449535896&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2008.03.001

DO - 10.1016/j.neurobiolaging.2008.03.001

M3 - Article

VL - 31

SP - 58

EP - 73

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 1

ER -