Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons

Catherine M. Cowan, Jimmy Thai, Stanislaw Krajewski, John C. Reed, Donald W. Nicholson, Scott H Kaufmann, A. Jane Roskams

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Caspase-9, an initiator caspase, and caspase-3, an effector caspase, have been suggested to mediate the terminal stages of neuronal apoptosis, but little is known about their activation in vivo. We examined temporal and spatial aspects of caspase-9 and -3 activation in olfactory receptor neurons (ORNs) undergoing apoptosis after target removal in vivo. After removal of the olfactory bulb, enhanced expression of procaspase-9 and -3 is observed in ORNs, followed by activation initially at the level of the lesion, then in axons, and only later in the ORN soma. We established the amyloid precursor-like protein-2 (APLP2) as a caspase substrate that is cleaved in an identical spatiotemporal pattern, suggesting its cleavage is the result of retrograde propagation of a pro-apoptotic signal in a caudorostral wave from the synapse through the axon to the ORN cell body. A null mutation in caspase-3 causes a change in axonal patterning indicative of an overall developmental expansion of the ORN population, and mature ORNs of caspase-3 knock-outs do not undergo caspase-dependent terminal dUTP nick end labeling-positive apoptosis after olfactory bulb removal. These results demonstrate that ORNs require caspase-3 activation to undergo normal developmental and mature target-deprived apoptosis. In addition, we demonstrate an axonal site of action for caspase-3 and -9 and show that regulation and activation of caspase-3 and -9 leading to apoptosis is a highly ordered process that occurs initially at the presynaptic level and only later at the cell body after deafferentation.

Original languageEnglish (US)
Pages (from-to)7099-7109
Number of pages11
JournalJournal of Neuroscience
Volume21
Issue number18
StatePublished - Sep 15 2001

Fingerprint

Olfactory Receptor Neurons
Caspase 9
Caspase 3
Synapses
Apoptosis
Olfactory Bulb
Caspases
Axons
Initiator Caspases
Effector Caspases
Cell Body
Amyloid beta-Protein Precursor
Carisoprodol
Mutation

Keywords

  • Amyloid precursor-like protein-2
  • Caspases
  • Degeneration
  • Neuronal apoptosis
  • Olfactory receptor neuron
  • Retrograde signaling

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cowan, C. M., Thai, J., Krajewski, S., Reed, J. C., Nicholson, D. W., Kaufmann, S. H., & Roskams, A. J. (2001). Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons. Journal of Neuroscience, 21(18), 7099-7109.

Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons. / Cowan, Catherine M.; Thai, Jimmy; Krajewski, Stanislaw; Reed, John C.; Nicholson, Donald W.; Kaufmann, Scott H; Roskams, A. Jane.

In: Journal of Neuroscience, Vol. 21, No. 18, 15.09.2001, p. 7099-7109.

Research output: Contribution to journalArticle

Cowan, CM, Thai, J, Krajewski, S, Reed, JC, Nicholson, DW, Kaufmann, SH & Roskams, AJ 2001, 'Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons', Journal of Neuroscience, vol. 21, no. 18, pp. 7099-7109.
Cowan CM, Thai J, Krajewski S, Reed JC, Nicholson DW, Kaufmann SH et al. Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons. Journal of Neuroscience. 2001 Sep 15;21(18):7099-7109.
Cowan, Catherine M. ; Thai, Jimmy ; Krajewski, Stanislaw ; Reed, John C. ; Nicholson, Donald W. ; Kaufmann, Scott H ; Roskams, A. Jane. / Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 18. pp. 7099-7109.
@article{2c68e1bed5fe47fcb5ee9e6c010d4005,
title = "Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons",
abstract = "Caspase-9, an initiator caspase, and caspase-3, an effector caspase, have been suggested to mediate the terminal stages of neuronal apoptosis, but little is known about their activation in vivo. We examined temporal and spatial aspects of caspase-9 and -3 activation in olfactory receptor neurons (ORNs) undergoing apoptosis after target removal in vivo. After removal of the olfactory bulb, enhanced expression of procaspase-9 and -3 is observed in ORNs, followed by activation initially at the level of the lesion, then in axons, and only later in the ORN soma. We established the amyloid precursor-like protein-2 (APLP2) as a caspase substrate that is cleaved in an identical spatiotemporal pattern, suggesting its cleavage is the result of retrograde propagation of a pro-apoptotic signal in a caudorostral wave from the synapse through the axon to the ORN cell body. A null mutation in caspase-3 causes a change in axonal patterning indicative of an overall developmental expansion of the ORN population, and mature ORNs of caspase-3 knock-outs do not undergo caspase-dependent terminal dUTP nick end labeling-positive apoptosis after olfactory bulb removal. These results demonstrate that ORNs require caspase-3 activation to undergo normal developmental and mature target-deprived apoptosis. In addition, we demonstrate an axonal site of action for caspase-3 and -9 and show that regulation and activation of caspase-3 and -9 leading to apoptosis is a highly ordered process that occurs initially at the presynaptic level and only later at the cell body after deafferentation.",
keywords = "Amyloid precursor-like protein-2, Caspases, Degeneration, Neuronal apoptosis, Olfactory receptor neuron, Retrograde signaling",
author = "Cowan, {Catherine M.} and Jimmy Thai and Stanislaw Krajewski and Reed, {John C.} and Nicholson, {Donald W.} and Kaufmann, {Scott H} and Roskams, {A. Jane}",
year = "2001",
month = "9",
day = "15",
language = "English (US)",
volume = "21",
pages = "7099--7109",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "18",

}

TY - JOUR

T1 - Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons

AU - Cowan, Catherine M.

AU - Thai, Jimmy

AU - Krajewski, Stanislaw

AU - Reed, John C.

AU - Nicholson, Donald W.

AU - Kaufmann, Scott H

AU - Roskams, A. Jane

PY - 2001/9/15

Y1 - 2001/9/15

N2 - Caspase-9, an initiator caspase, and caspase-3, an effector caspase, have been suggested to mediate the terminal stages of neuronal apoptosis, but little is known about their activation in vivo. We examined temporal and spatial aspects of caspase-9 and -3 activation in olfactory receptor neurons (ORNs) undergoing apoptosis after target removal in vivo. After removal of the olfactory bulb, enhanced expression of procaspase-9 and -3 is observed in ORNs, followed by activation initially at the level of the lesion, then in axons, and only later in the ORN soma. We established the amyloid precursor-like protein-2 (APLP2) as a caspase substrate that is cleaved in an identical spatiotemporal pattern, suggesting its cleavage is the result of retrograde propagation of a pro-apoptotic signal in a caudorostral wave from the synapse through the axon to the ORN cell body. A null mutation in caspase-3 causes a change in axonal patterning indicative of an overall developmental expansion of the ORN population, and mature ORNs of caspase-3 knock-outs do not undergo caspase-dependent terminal dUTP nick end labeling-positive apoptosis after olfactory bulb removal. These results demonstrate that ORNs require caspase-3 activation to undergo normal developmental and mature target-deprived apoptosis. In addition, we demonstrate an axonal site of action for caspase-3 and -9 and show that regulation and activation of caspase-3 and -9 leading to apoptosis is a highly ordered process that occurs initially at the presynaptic level and only later at the cell body after deafferentation.

AB - Caspase-9, an initiator caspase, and caspase-3, an effector caspase, have been suggested to mediate the terminal stages of neuronal apoptosis, but little is known about their activation in vivo. We examined temporal and spatial aspects of caspase-9 and -3 activation in olfactory receptor neurons (ORNs) undergoing apoptosis after target removal in vivo. After removal of the olfactory bulb, enhanced expression of procaspase-9 and -3 is observed in ORNs, followed by activation initially at the level of the lesion, then in axons, and only later in the ORN soma. We established the amyloid precursor-like protein-2 (APLP2) as a caspase substrate that is cleaved in an identical spatiotemporal pattern, suggesting its cleavage is the result of retrograde propagation of a pro-apoptotic signal in a caudorostral wave from the synapse through the axon to the ORN cell body. A null mutation in caspase-3 causes a change in axonal patterning indicative of an overall developmental expansion of the ORN population, and mature ORNs of caspase-3 knock-outs do not undergo caspase-dependent terminal dUTP nick end labeling-positive apoptosis after olfactory bulb removal. These results demonstrate that ORNs require caspase-3 activation to undergo normal developmental and mature target-deprived apoptosis. In addition, we demonstrate an axonal site of action for caspase-3 and -9 and show that regulation and activation of caspase-3 and -9 leading to apoptosis is a highly ordered process that occurs initially at the presynaptic level and only later at the cell body after deafferentation.

KW - Amyloid precursor-like protein-2

KW - Caspases

KW - Degeneration

KW - Neuronal apoptosis

KW - Olfactory receptor neuron

KW - Retrograde signaling

UR - http://www.scopus.com/inward/record.url?scp=0035884951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035884951&partnerID=8YFLogxK

M3 - Article

C2 - 11549720

AN - SCOPUS:0035884951

VL - 21

SP - 7099

EP - 7109

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 18

ER -