Genes for neurotrophic factors and their receptors: structure and regulation

Metsis, Madis

doi:10.1007/pl00000916

Cited by 16 publications

(17 citation statements)

References 48 publications

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“…mRNA was aligned across species using mVISTA (http://genome.lbl.gov/vista/mvista/submit.shtml), and phylogenetic trees were constructed [21]–[33]. NCBI's Blastn and Blastp were used to compare nucleotide and protein identities and gaps between species.…”

Section: Methodsmentioning

confidence: 99%

“…As for Ntrk2, a comprehensive analysis of Ntrk2 immunoreactivity was assessed and it was found to be expressed mainly in glandular cells of the salivary gland, small intestine, colon, endocrine pancreas, bone marrow hematopoietic cells, monocytes/macrophages of the lymph nodes and spleen, and in the epidermis [15]. Previous studies have shown that neurotrophins in the brain are regulated by neuronal activity (Ca++ influx induced transcription) [16], and steroid hormones [17]–[20], and that tissue-specific expression is driven by multiple promoters [21].…”

Section: Introductionmentioning

confidence: 99%

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The Brain-Uterus Connection: Brain Derived Neurotrophic Factor (BDNF) and Its Receptor (Ntrk2) Are Conserved in the Mammalian Uterus

Wessels

Leyland

et al. 2014

PLoS ONE

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The neurotrophins are neuropeptides that are potent regulators of neurite growth and survival. Although mainly studied in the brain and nervous system, recent reports have shown that neurotrophins are expressed in multiple target tissues and cell types throughout the body. Additionally, dysregulation of neurotrophins has been linked to several disease conditions including Alzheimer's, Parkinson's, Huntington's, psychiatric disorders, and cancer. Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that elicits its actions through the neurotrophic tyrosine receptor kinase type 2 (Ntrk2). Together BDNF and Ntrk2 are capable of activating the adhesion, angiogenesis, apoptosis, and proliferation pathways. These pathways are prominently involved in reproductive physiology, yet a cross-species examination of BDNF and Ntrk2 expression in the mammalian uterus is lacking. Herein we demonstrated the conserved nature of BDNF and Ntrk2 across several mammalian species by mRNA and protein sequence alignment, isolated BDNF and Ntrk2 transcripts in the uterus by Real-Time PCR, localized both proteins to the glandular and luminal epithelium, vascular smooth muscle, and myometrium of the uterus, determined that the major isoforms expressed in the human endometrium were pro-BDNF, and truncated Ntrk2, and finally demonstrated antibody specificity. Our findings suggest that BDNF and Ntrk2 are transcribed, translated, and conserved across mammalian species including human, mouse, rat, pig, horse, and the bat.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Brain-Uterus Connection: Brain Derived Neurotrophic Factor (BDNF) and Its Receptor (Ntrk2) Are Conserved in the Mammalian Uterus

Wessels

Leyland

et al. 2014

PLoS ONE

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show abstract

“…This gene contains 16 introns of 70bp to 3.3kb and 17 exons of 18 to 394bp (Indo et al, 1997), with the 9 first exons encoding for the extracellular part of the receptor (Metsis, 2001). The TrkA protein contains 790 amino acids with a molecular weight of 140 kDa (Meakin & Shooter, 1992), and is composed of an intracellular domain containing a tyrosine-kinase intrinsic activity, a unique transmembrane helix, and an extracellular domain dedicated to NGF binding (Wiesmann & de Vos, 2001).…”

Section: Structure Of the Trka Receptormentioning

confidence: 99%

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

Freund-Michel¹,

Müller²,

Frossard³

2011

Inflammatory Diseases - A Modern Perspective

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“…Owing to its role in multiple cellular activities, Trk receptor expression is regulated at the level of transcription (10), mRNA stability (11) and protein half-life (12). However, regulation of Trk receptor protein synthesis is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Internal initiation of translation of the TrkB mRNA is mediated by multiple regions within the 5' leader

Dobson¹

2005

Nucleic Acids Research

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Translational regulation of the dendritically localized mRNA encoding for the neurotrophin receptor TrkB has important ramifications for synaptic function. We examined whether the TrkB mRNA is translated through an internal initiation entry site (IRES). The human TrkB 5′ leaders are derived from the use of alternative promoters and alternative splicing, but all 5′ leaders share a common exon. Insertion of a full-length 5′ leader, as well as the common exon into the intercistronic region of a dicistronic luciferase construct, yielded luciferase activity generated from the second cistron that was either equivalent or higher than that observed from the encephalomyocarditis virus IRES. Moreover, inhibiting cap-dependent translation ex vivo and in in vitro lysates had only a minimal effect on the translation of mRNA containing the TrkB 5′ leader. Dissecting the 5′ leader showed that the IRES is located in the exon common to all TrkB 5′ leaders. Moreover, six regions ranging from 2 to 25 nt were identified that either promoted or inhibited IRES activity. Taken together, these results suggest that the 5′ leader of the human TrkB mRNA contains multiple cis-elements that regulate internal initiation of translation and that this mechanism may contribute significantly to the translation of the TrkB mRNA in neuronal dendrites.

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Genes for neurotrophic factors and their receptors: structure and regulation

Cited by 16 publications

References 48 publications

The Brain-Uterus Connection: Brain Derived Neurotrophic Factor (BDNF) and Its Receptor (Ntrk2) Are Conserved in the Mammalian Uterus

The Brain-Uterus Connection: Brain Derived Neurotrophic Factor (BDNF) and Its Receptor (Ntrk2) Are Conserved in the Mammalian Uterus

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

Internal initiation of translation of the TrkB mRNA is mediated by multiple regions within the 5' leader

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