Novel transcripts reveal a complex structure of the human TRKA gene and imply the presence of multiple protein isoforms. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Luberg, Kristi; Park, Rahel; Aleksejeva, Elina; Timmusk, Tõnis
• Is Part Of: BMC neuroscience. Volume 16:Issue 1(2015)
• Page Start: 1
• Page End: 21
• Publication Date: 2015-12
• Subjects: TRKA -- NTRK1 -- 5′ RACE -- Glycosylation -- Nuclear localization -- Isoforms -- Alternative splicing; Neurosciences -- Periodicals; 573.805
• DOI: 10.1186/s12868-015-0215-x
• Languages: English
• ISSNs: 1471-2202

Abstract

Abstract Background Tropomyosin-related kinase A (TRKA) is a nerve growth factor (NGF) receptor that belongs to the tyrosine kinase receptor family. It is critical for the correct development of many types of neurons including pain-mediating sensory neurons and also controls proliferation, differentiation and survival of many neuronal and non-neuronal cells.TRKA (also known asNTRK1 ) gene is a target of alternative splicing which can result in several different protein isoforms. Presently, three human isoforms (TRKAI, TRKAII and TRKAIII) and two rat isoforms (TRKA L0 and TRKA L1) have been described. Results We show here that humanTRKA gene is overlapped by two genes and spans 67 kb—almost three times the size that has been previously described. Numerous transcription initiation sites from eight different 5′ exons and a sophisticated splicing pattern among exons encoding the extracellular part of TRKA receptor indicate that there might be a large variety of alternative protein isoforms.TrkA genes in rat and mouse appear to be considerably shorter, are not overlapped by other genes and display more straightforward splicing patterns. We describe the expression profile of alternatively splicedTRKA transcripts in different tissues of human, rat and mouse, as well as analyze putative endogenous TRKA protein isoforms in human SH-SY5Y and rat PC12 cells. We also characterize a selection of novel putative protein isoforms by portraying their phosphorylation, glycosylation and intracellular localization patterns. Our findings show that an isoform comprising mainly of TRKA kinase domain is capable of entering the nucleus. Conclusions Results obtained in this study refer to the existence of a multitude ofTRKA mRNA and protein isoforms, with some putative proteins possessing very distinct properties.