Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins

Curtis, Rory; Adryan, Krystyna M.; Stark, Jennifer; Park, John S.; Compton, Debra L; Weskamp, Gisela; Huber, Lysiane; Chao, Moses V.; Jaenisch, Rudolf; Lee, Kuo‐Fen; Lindsay, Ronald M.; DiStefano, Peter S.

doi:10.1016/0896-6273(95)90267-8

Cited by 207 publications

(135 citation statements)

References 61 publications

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“…In contrast, NT4/5 can also bind efficiently to the NT3 high-affinity sites (Fig. 3), in line with previous studies using neurotrophin mutants (Rydén et al, 1995) and retrograde transport in vivo (Curtis et al, 1995), indicating a selective interaction of NT4/5 with p75 N TR .…”

Section: Neuronal P75 Ntr Forms High-affinity Selective Nt3 Receptorssupporting

confidence: 72%

The Neurotrophin Receptor p75 Binds Neurotrophin-3 on Sympathetic Neurons with High Affinity and Specificity

Dechant¹,

Tsoulfas

Parada

et al. 1997

J. Neurosci.

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High-affinity neurotrophin-3 (NT3) receptors have been identified on nerve growth factor (NGF)-dependent sympathetic neurons, but their occupancy by NT3 does not lead to neuronal survival. The molecular nature of these NT3 binding sites was investigated in this study. With freshly dissociated embryonic day 11 (E11) chick sympathetic neurons, cross-linking experiments revealed that the main receptor responsible for highaffinity specific binding was the neurotrophin receptor p75 (p75 NTR ), with only a small fraction corresponding to trkC. When E11 sympathetic neurons were cultured in the presence of NGF, trkC transcripts became undetectable, but high-affinity specific NT3 binding persisted. Cross-linking and antibody inhibition experiments indicated that p75 NTR was the only detectable NT3 receptor protein. These characteristics were not observed when p75 NTR was expressed in transformed cells. We conclude that p75 NTR can exist in neurons in a confirmation conferring hitherto unrecognized properties to this receptor.

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Section: Neuronal P75 Ntr Forms High-affinity Selective Nt3 Receptorssupporting

confidence: 72%

The Neurotrophin Receptor p75 Binds Neurotrophin-3 on Sympathetic Neurons with High Affinity and Specificity

Dechant¹,

Tsoulfas

Parada

et al. 1997

J. Neurosci.

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“…Excess BDNF vesicles transported to the neurite terminal that are not captured by stimulation would then be expected to return to the cell body for degradation, or perhaps even reuse, to maintain homeostasis. While retrograde transport of BDNF from the postsynaptic terminal has been reported (Bhattacharyya et al, 2002;Curtis et al, 1995;DiStefano et al, 1992;Reynolds et al, 2000;Yano and Chao, 2004), it is unlikely that the BDNF-GFP vesicles we observed moving in the retrograde direction in hippocampal neurons represent vesicles that was released and endocytosed, since we were studying unstimulated neurons. Besides, the BDNF-GFP signal in such putative vesicles, if generated, would be far too weak to be detected.…”

Section: Discussionmentioning

confidence: 89%

A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons

Park

Cawley

Loh

2008

Molecular and Cellular Neuroscience

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Anterograde transport of brain-derived neurotrophic factor (BDNF) vesicles from the soma to neurite terminals is necessary for activity-dependent secretion of BDNF to mediate synaptic plasticity, memory and learning, and retrograde BDNF transport back to the soma for recycling. In our study, overexpression of the cytoplasmic tail of the carboxypeptidase E (CPE) found in BDNF vesicles significantly reduced localization of BDNF in neurites of hippocampal neurons. Live-cell imaging showed that the velocity and distance of movement of fluorescent protein-tagged CPE-or BDNFcontaining vesicles were reduced in both directions. In pull-down assays, the CPE tail interacted with dynactin along with kinesin-2 and kinesin-3, and cytoplasmic dynein. Competition assays using a CPE tail peptide verified specific interaction between the CPE tail and dynactin. Thus, the CPE cytoplasmic tail binds dynactin that recruits kinesins or dynein for driving bi-directional transport of BDNF vesicle to maintain vesicle homeostasis and secretion in hippocampal neurons.

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“…p75 NTR is internalized and retrogradely transported, but it does not appear to be down-regulated from the cell surface in response to NGF (M.G., D. Hall, A. Schroepfel, and W.M., unpublished observations) (63)(64)(65). Moreover, p75 NTR does not appear to play a significant role in the retrograde transport of NGF, but does transport other neurotrophins (66,67). These findings suggest that p75 NTR does not play a role in survival-promoting retrograde signaling by NGF.…”

Section: Resultsmentioning

confidence: 99%

A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA

Grimes

Beattie²,

Mobley³

1997

Proc. Natl. Acad. Sci. U.S.A.

159

138

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The topology of signal transduction is particularly important for neurons. Neurotrophic factors such as nerve growth factor (NGF) interact with receptors at distal axons and a signal is transduced by retrograde transport to the cell body to ensure survival of the neuron. We have discovered an organelle that may account for the retrograde transport of the neurotrophin signal. This organelle is derived from endocytosis of the receptor tyrosine kinase for NGF, TrkA. In vitro reactions containing semi-intact PC12 cells and ATP were used to enhance recovery of a novel organelle: small vesicles containing internalized NGF bound to activated TrkA. These vesicles were distinct from clathrin coated vesicles, uncoated primary endocytic vesicles, and synaptic vesicles, and resembled transport vesicles in their sedimentation velocity. They contained 10% of the total bound NGF and almost one-third of the total tyrosine phosphorylated TrkA. These small vesicles are compelling candidates for the organelles through which the neurotrophin signal is conveyed down the axon.

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Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins

Cited by 207 publications

References 61 publications

The Neurotrophin Receptor p75 Binds Neurotrophin-3 on Sympathetic Neurons with High Affinity and Specificity

The Neurotrophin Receptor p75 Binds Neurotrophin-3 on Sympathetic Neurons with High Affinity and Specificity

A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons

A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA

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