biology

Low-affinity nerve growth factor receptor

Low-affinity nerve growth factor receptor is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Low-affinity nerve growth factor receptor rather than just read about it. In short: The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4.

Key takeaways

Low-affinity nerve growth factor receptor belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Low-affinity nerve growth factor receptor to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Low-affinity nerve growth factor receptor from memory before moving on to harder problems.

Reference excerpt

The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.

Receptor family p75NTR is a member of the tumor necrosis factor receptor superfamily. p75NTR/LNGFR was the first member of this large family of receptors to be characterized, that now contains about 25 receptors, including tumor necrosis factor 1 (TNFR1) and TNFR2, Fas, RANK, and CD40. All members of the TNFR superfamily contain structurally related cysteine-rich modules in their ECDs. p75NTR is an unusual member of this family due to its propensity to dimerize rather than trimerize, because of its ability to act as a tyrosine kinase co-receptor, and because the neurotrophins are structurally unrelated to the ligands, which typically bind TNFR family members. Indeed, with the exception of p75NTR, essentially all members of the TNFR family preferentially bind structurally related trimeric Type II transmembrane ligands, members of the TNF ligand superfamily.

Structure p75NTR is a type I transmembrane protein, with a molecular weight of 75 kDa, determined by glycosylation through both N- and O-linkages in the extracellular domain. It consists of an extracellular domain, a transmembrane domain and an intracellular domain. The extracellular domain consists of a stalk domain connecting the transmembrane domain and four cysteine-rich repeat domains, CRD1, CRD2, CRD3, and CRD4; which are negatively charged, a property that facilitates Neurotrophin binding. The intracellular part is a global-like domain, known as a death domain, which consists of two sets of perpendicular helixes arranged in sets of three. It connects the transmembrane domain through a flexible linker region N-terminal domain. It is important to say that, in contrast to the type I death domain found in other TNFR proteins, the type II intracellular death domain of p75NTR does not self-associate. This was an early indication that p75NTR does not signal death through the same mechanism as the TNFR death domains, although the ability of the p75NTR death domain to activate other second messengers is conserved. The p75ECD-binding interface to NT-3 can be divided into three main contact sites, two in the case of NGF, that are stabilized by hydrophobic interactions, salt bridges, and hydrogen bonds. The junction regions between CDR1 and CDR2 form the site 1 that contains five hydrogen bonds and one salt bridge. Site 2 is formed by equal contributions from CDR3 and CRD4 and involves two salt bridges and two hydrogen bonds. Site 3, in the CRD4, includes only one salt bridge.

Function

Interactions with neurotrophins Neurotrophins that interact with p75NTR include NGF, NT-3, BDNF, and NT-4/5. Neurotrophins activating p75NTR may initiate apoptosis (for example, via c-Jun N-terminal kinases signaling, and subsequent p53, Jax-like proteins and caspase activation). This effect can be counteracted by anti-apoptotic signaling by TrkA. Neurotrophin binding to p75NTR, in addition to apoptotic signaling, can also promote neuronal survival (for example, via NF-kB activation). There are multiple targets of Akt that could play a role in mediating p75NTR-dependent survival, but one of the more intriguing possibilities is that Ant-induced phosphorylation of IkB kinase 1 (IKK1) plays a role in the induction of NF-kB.

Interactions with proneurotrophins Proforms of NGF and BDNF (proNGF and proBDNF) are precursors to NGF and BDNF. proNGF and proBDNF interact with p75NTR and cause p75NTR-mediated apoptosis without activating TrkA-mediated survival mechanisms. Cleavage of proforms into mature Neurotrophins allows the mature NGF and BDNF to activate TrkA-mediated survival mechanisms.

Sensory development Recent research has suggested a number of roles for the LNGFR, including in development of the eyes and sensory neurons, and in repair of muscle and nerve damage in adults. Two distinct subpopulations of Olfactory ensheathing glia have been identified with high or low cell surface expression of low-affinity nerve growth factor receptor (p75).

Interactions with other receptors

Sortilin Sortilin is required for many apoptosis-promoting p75NTR reactions, functioning as a co-receptor for the binding of neurotrophins such as BDNF. pro-neurotrophins (such as proBDNF) bind especially well to p75NTR when sortilin is present.

Crosstalk with Trk receptors When p75NTR initiates apoptosis, NGF binding to Tropomyosin receptor kinase A (TrkA) can negate p75NTR apoptotic effects. p75NTR c-Jun kinase pathway activation (which causes apoptosis) is suppressed when NGF binds to TrkA. p75NTR activation of NF-kB, which promotes survival, is unaffected by NGF binding to TrkA.

Nogo-66 receptor (NgR1) p75NTR functions in a complex with Nogo-66 receptor (NgR1) to mediate RhoA-dependent inhibition of growth of regenerating axons exposed to inhibitory proteins of CNS myelin, such as Nogo, MAG or OMgP. Without p75NTR, OMgP can activate RhoA and inhibit CNS axon regeneration. Coexpression of p75NTR and OMgP suppress RhoA activation. A complex of NgR1, p75NTR and LINGO1 can activate RhoA.

p75NTR-mediated signaling pathways

NF-kB activation NF-kB is a transcription factor that can be activated by p75NTR. Nerve growth factor (NGF) is a neurotrophin that promotes neuronal growth, and, in the absence of NGF, neurons die. Neuronal death in the absence of NGF can be prevented by NF-kB activation. Phosphorylated IκB kinase binds to and activates NF-kB before separating from NF-kB. After separation, IκB degrades and NF-kB continues to the nucleus to initiate pro-survival transcription. NF-kB also promotes neuronal survival in conjunction with NGF. NF-kB activity is activated by p75NTR, and is not activated via Trk receptors. NF-kB activity does not effect Brain-derived neurotrophic factor promotion of neuronal survival.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Low-affinity nerve growth factor receptor

Start with the simplest possible case. Write down what Low-affinity nerve growth factor receptor claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Low-affinity nerve growth factor receptor before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Low-affinity nerve growth factor receptor ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Low-affinity nerve growth factor receptor

In research: Low-affinity nerve growth factor receptor appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Low-affinity nerve growth factor receptor in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Low-affinity nerve growth factor receptor is common in secondary-school and first-year university syllabi. It links to neighbouring topics Clusters of differentiation, Genes on human chromosome 17, Neurochemistry, so understanding it makes those chapters shorter.
In everyday life: Look for Low-affinity nerve growth factor receptor outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Ask Teacher Smith questions about this articleOpens your AI tutor with a question about “Low-affinity nerve growth factor receptor” →

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Low-affinity nerve growth factor receptor in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Low-affinity nerve growth factor receptor means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Low-affinity nerve growth factor receptor out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Low-affinity nerve growth factor receptor in simple terms?

Why does Low-affinity nerve growth factor receptor matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Low-affinity nerve growth factor receptor?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Low-affinity nerve growth factor receptor.