Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development

Abstract

J. Neurochem. (2010) 113, 952–964. Abstract Brain‐derived neurotrophic factor and neurotrophin‐4 high‐affinity receptor tropomyosine related kinase (Trk) B is required for the differentiation and maintenance of specific neuron populations. Misregulation of TrkB has been reported in many human diseases, including cancer, obesity and neurological and psychiatric disorders. Alternative splicing that generates receptor isoforms with different functional properties also regulates TrkB function. Here, we describe numerous novel isoforms of TrkB proteins, including isoforms generated by alternative splicing of cassette exons in the regions encoding both the extracellular and intracellular domain and also N‐terminally truncated isoforms encoded by novel 5′ exon‐containing transcripts. We also characterize the intracellular localization and phosphorylation potential of novel TrkB isoforms and find that these proteins have unique properties. In addition, we describe the expression profiles of all the known human TrkB transcripts in adult tissues and also during postnatal development in the human prefrontal cortex. We show that transcripts encoding the full‐length TrkB receptor and the C‐terminally truncated TrkB‐T1 have different expression profiles as compared to the proteins they encode. Identification of 36 potential TrkB protein isoforms suggests high complexity in the synthesis, regulation and function of this important neurotrophin receptor emphasizing the need for further study of these novel TrkB variants.

Defect of tropomyosin-related kinase B isotype expression in ovarian clear cell adenocarcinoma

“…The absence of exons 18-19 (TrkB-T-Shc) was also observed in MA (1/8). The transmembrane domain (exon [12][13][14] and the TK domain (exon [22][23] were detected in all ovarian adenocarcinomas (OAs), suggesting the importance of these domains for TrkB expression. BDNF mRNA was expressed in all OAs, and no differences were observed in relation to the histology or clinical stage.…”

“…These truncated isoforms, TrkB-T-Shc and TrkB-T1, may function in normal neuronal tissues to modulate the TrkB signal. Moreover, TrkB isoforms lacking several exons at the N-terminus have recently been predicted by in silico analysis (13).…”

Bridging the Gap between Genes and Behavior: Brain-Derived Neurotrophic Factor and the mTOR Pathway in Idiopathic Autism

“…They thus may act as negative regulators of BDNF signaling [90]. Neurotrophic effects of BDNF depend on the relative levels of TrkB isoforms [89,91,92].…”

Melanoma and the Nervous System – Novel Pathways Mediated by Neurotrophins and Their Receptors

“…36 novel isoforms of TrkB proteins with unique properties have been described recently. This suggests high complexity in the synthesis, regulation and function of this important NTs receptor, emphasizing the need for further study of these novel TrkB variants (Luberg et al, 2010). TrkC has several characteristics of a tumor suppressor: its expression in tumors has often been associated with good prognosis.…”