Neurotrophin Receptors

Type of Neurotrophin receptors

Neurotrophin binding to neurons is comprised of 'high-affinity' Neurotrophin receptorand 'low-affinity' Neurotrophin receptor. The high attinity Neurotrophin receptor is Trk family which belongs to neurotrophic tyrosine kinase receptors. Trk family consists of TrkA, TrkB and TrkC. NGF binds to TrkA, BDNF and NT-4 bind to TrkB and NT-3 binds to TrkC. In addition NT-3 also binds to and activates TrkA and TrkB but it does so less efficiently. The low affinity Neurotrophin receptor is NGFR, also named p75 or p75 NTR, to which all neurotrophins bind.

Trk receptor structure and neurotrophin binding

Trk receptors is a kind of Neurotrophin receptor contain an extracellular domain composed of three leucine-rich motifs flanked by two cysteine clusters, two immunoglobulin-like C2 type domains (Ig-C2), a single transmembrane domain, and a cytoplasmic region with a kinase domain (Fig. 1). Binding of neurotrophins to Trk receptors occurs mainly through the Ig-C2 domains, as described using chimeras between different Neurotrophin receptors, deletions, and point mutation analyses, with the domain closer to the transmembrane region playing a more prominent role. In addition to ligand binding, the Ig-C2 domains can also stabilize the monomeric form of the Trk receptor to prevent spontaneous dimerization and activation in the absence of neurotrophins. The structures of NGF alone and in complex with the second Ig-C2 have been resolved. The affinity of neurotrophins to TrkA and TrkB receptors is modulated by the presence of p75NTR, which enhances specificity for their primary ligands NGF and BDNF, respectively. Formation of high-affinity binding sites for NGF requires the presence of a correct ratio of Neurotrophin receptor, as mutations of the cytoplasmic or transmembrane domains of either TrkA or p75NTR abolish the configuration of high-affinity binding sites. At the same time, p75NTR reduces the ability of NT- 3 to activate TrkA, and NT-3 and NT-4 to activate TrkB. This effect has been recently demonstrated.

NGFR receptor structure and neurotrophin binding

The NGFR integral membrane protein is the founding member of the TNF family of receptors, and contains a cysteine-rich domain and a cytoplasmic death domain ( Fig. 1 ). The nuclear magnetic resonance structure of the intracellular p75NTR region shows a flexible juxtamembrane region and a death domain that consists of two perpendicular sets of three helices packed into a globular structure. The lack of self-association of the intracellular region of p75NTR differentiates the activation of this receptor from that of TNF and Fas receptors, which require aggregation for proper signaling. The crystal structure of NGF in complex with the extracellular domain of p75NTR has been recently solved, revealing a surprising 2:1 NGF: p75NTR stoichiometry that is unlike the trimeric ligand-receptor complexes of the other TNF receptor family members. Binding of an NGF dimer to one molecule of p75NTR induces conformational changes in the NGF protein that prevents the association of a second p75NTR molecule. The observed 2:1 NGF: p75NTR ratio may allow other Neurotrophin receptors to be recruited to form higher-order complexes. Indeed, p75NTR can form high-affinity sites with Trk receptors.

Neurotrophin and Neurotrophin receptors
23000+ Products
Proteins
Antibodies
ELISA Kits
cDNA Clones
Recombinant Cytokines
Neurotrophin & Receptor
NGF Related Information +
- NGF molecular weight
- NGF structure
- NGF function
- NGF signaling / pathway
- NGF receptor
-- NGF TrkA
-- NGFR / p75
BDNF Related Information +
- BDNF Gene
- BDNF function
- BDNF signaling / pathway
- BDNF receptor
-- BDNF TrkB
-- NGFR / p75
• Other Neurotrophin & Receptor+
- Neurotrophin-3 / NT-3
- TrkA / NTRK1
- TrkB / NTRK2
- TrkC / NTRK3
- NGFR (p75 / p75 NTR)
GDNF Family
GDNF (Glial cell line-derived neurotrophin)
GFRA1
GFRA2
GFRA3
NCAM / CD56
Other Neurotrophic Factors & Receptors
MANF / ARMET
Gp130 / IL6ST
LIFR / CD118
CNTF / Ciliary Neurotrophic Factor
CDNF / ARMETL1
NRG1 / Neuregulin 1
NRG4 / Neuregulin 4
Pleiotrophin / PTN
CNTFR
Growth Factor Family
Angiopoietin/Tie
Ephrin & Eph Receptor
EGF & Receptor
FGF & Receptor
Insulin-like Growth Factor System
Neurotrophin & Receptor
PDGF & Receptor
Receptor Tyrosine Kinase
R-Spondin Protein
VEGF & Receptor
Wnt Ligands & Receptors