Developmental and mature expression of full-length and truncated TrkB, receptors in the rat forebrain

Fryer, Robert H.; Kaplan, David R.; Feinstein, Stuart C.; Radeke, Monte J.; Grayson, Dennis R.; Kromer, Lawrence F.

doi:10.1002/(sici)1096-9861(19961007)374:1<21::aid-cne2>3.0.co;2-p

Cited by 260 publications

(170 citation statements)

References 76 publications

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“…The full-length TrkB protein decreased slightly, after an initial increase from E18 to P2, and the truncated protein increased during development. The increase in the full-length TrkB from embryo to early postnatal ages, and the increase in the truncated protein through postnatal development are consistent with published findings (Escandón et al, 1994;Fryer et al, 1996). Only a low level was evident in the P2 PSD II fraction; the only band in this fraction was the full-length form as described for adult brain PSDs (Wu et al, 1996).…”

Section: Trkbsupporting

confidence: 90%

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

209

196

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In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluRassociated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors and CaMKII. Other components showed more moderate changes.

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Section: Trkbsupporting

confidence: 90%

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

209

196

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“…Even though T1 is mostly expressed in non-neuronal cells in the central nervous system, it has been shown to colocalize with TKϩ in a subpopulation of hippocampal as well as motor neurons (24,(31)(32)(33). TKϪ forms inhibit TKϩ signaling by sequestering BDNF when expressed in nonneuronal cells (32)(33)(34)(35)(36) or functioning as dominant negative receptors by heterodimerization when coexpressed together with TKϩ in the same cells (37)(38)(39)(40). The recently cloned truncated T-Shc contains an Shc-binding site in the juxtamembrane domain similar to TKϩ, but it lacks the kinase domain and has a unique truncated C terminus (30).…”

supporting

confidence: 57%

Regulation of TRKB Surface Expression by Brain-derived Neurotrophic Factor and Truncated TRKB Isoforms

Haapasalo¹,

Sipola²,

Larsson³

et al. 2002

Journal of Biological Chemistry

150

110

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Brain-derived neurotrophic factor (BDNF) signaling through its receptor TRKB modulates survival, differentiation, and activity of neurons. BDNF activates TRKB on the cell surface, which leads to the initiation of intracellular signaling cascades and different biological responses in neurons. Neuronal activity has been shown to regulate TRKB levels on the plasma membrane of neurons, but little is known about other factors affecting TRKB surface expression levels. We report here that BDNF regulates the cell surface levels of transfected or endogenously expressed full-length TRKB, depending on the exposure time in neuroblastoma cells and primary hippocampal neurons. BDNF rapidly increases TRKB surface expression levels in seconds, whereas treatment of cells with BDNF for a longer time (minutes to hours) leads to decreased TRKB surface levels. Coexpression of the full-length TRKB together with the truncated TRKB.T1 isoform results in decreased levels of fulllength TRKB on the cell surface. This effect is specific to the T1 isoform, because coexpression of a kinase-dead TRKB mutant or another kinase domain-lacking TRKB form, truncated T-Shc, leads to increased TRKB surface levels. Our results suggest that regulation of TRKB surface expression levels by different factors is tightly controlled by complex mechanisms in active neurons. Neurotrophin brain-derived neurotrophic factor (BDNF) 1 is a key regulator of survival and differentiation of specific neuronal populations in the central nervous system (1, 2). In addition, increasing evidence indicates that BDNF plays important roles in regulating neuronal activity and synaptic events related to plasticity (for reviews, see Refs. 3-5). BDNF is released in an activity-dependent manner (6 -10), and it regulates neurotransmitter release and synaptic transmission of neurons (11-17).The biological effects of BDNF are mediated by TRKB transmembrane tyrosine kinase receptors (18 -23). The high affinity full-length TRKB.TKϩ (TKϩ) receptors are exclusively expressed in neurons in the central nervous system (24). Binding of BDNF to TRKB.TKϩ activates it by inducing dimerization and autophosphorylation at specific tyrosine residues in the cytoplasmic kinase domains (25). The phosphorylated tyrosines serve as docking sites to cytoplasmic effector molecules, which activate different signaling pathways that eventually lead to changes in gene expression and different biological responses in neurons (26).BDNF signaling through the TKϩ receptors can be modulated by the low affinity p75 neurotrophin receptor (27-29) but also by truncated TRKB isoforms (TKϪ; see Refs. 20 and 24).Different TRKB isoforms are generated by alternative splicing resulting in the TKϩ form and three TKϪ splice variants: T1, T2, and T-Shc (20,24,30). Truncated T1 lacks the kinase domain but contains short isoform-specific cytoplasmic domain in its place (20,24). Even though T1 is mostly expressed in non-neuronal cells in the central nervous system, it has been shown to colocalize with TKϩ in a subpopulation of hipp...

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“…Fryer et al, 1996), the extracellular domain of TrkC (courtesy of Dr. F. Lefcort) (cf. Lefcort et al, 1996), the extracellular domain of p75 (the low-affinity neurotrophin receptor, courtesy of Dr. L. F. Reichardt) (cf.…”

Section: Immunohistochemistry For Neurotrophins and Trk Receptorsmentioning

confidence: 91%

Neurotrophins Suppress Apoptosis Induced by Deafferentation of an Avian Motor-Cortical Region

et al. 1997

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Studies of the developing nervous system led to the general view that growth factors promote neuronal survival in a "retrograde" manner. For example, release of NGF from postsynaptic peripheral targets followed by uptake and retrograde transport by presynaptic neurons provided a widely accepted conceptual framework for the action of neurotrophins. In contrast, although presynaptic or "anterograde" influences on the survival of developing neurons have been recognized for some time, the mechanisms by which afferent input regulates the survival of postsynaptic cells have received considerably less attention. In the forebrain network for learned vocal behavior in zebra finches, lesions of a cortical region for song control, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), remove presynaptic input to a motor-cortical song region, the robust nucleus of the archistriatum (RA), and cause massive RA neuron death in young birds that are entering the sensitive period for song learning. Here we report that lesions of lMAN followed by infusions of neurotrophins directly into RA completely suppress neuronal apoptosis in RA. Moreover, we show that lMAN neurons are able to transport neurotrophins in the anterograde direction to RA, that neurotrophin-like immunoreactivity is present in cells in lMAN and RA, and that neurotrophin receptor-like immunoreactivity is present in RA. Expression of neurotrophins in lMAN and RA suggests that lMAN presynaptic input could regulate RA neuron survival by synthesizing, transporting, and releasing neurotrophins anterogradely or by regulating the auto/paracrine release of neurotrophins within RA, or perhaps by both. These data provide the first in vivo demonstration that neurotrophins can prevent the death of deafferented cortical neurons, and they raise the possibility that nonretrograde signaling by neurotrophins may be a common means of promoting neuronal survival in the vertebrate telencephalon. Anterograde and auto/ paracrine neurotrophin signaling, along with the more established view that neurotrophins regulate neuron survival via retrograde mechanisms, suggests multidirectional neurotrophin signaling in the vertebrate telencephalon.

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Developmental and mature expression of full-length and truncated TrkB, receptors in the rat forebrain

Cited by 260 publications

References 76 publications

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Regulation of TRKB Surface Expression by Brain-derived Neurotrophic Factor and Truncated TRKB Isoforms

Neurotrophins Suppress Apoptosis Induced by Deafferentation of an Avian Motor-Cortical Region

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