Identification and characterization of a neuron-specific isoform of protrudin
Open accessAbstract
Protrudin is a membrane protein that regulates polarized vesicular transport. Now, we have identified a novel isoform of protrudin (protrudin‐L) that contains an additional seven amino acids between the FFAT motif and the coiled‐coil domain compared with the conventional isoform (protrudin‐S) as a result of alternative splicing of a microexon (exon L). Protrudin‐L mRNA was found to be mostly restricted to the central nervous system in mice, whereas protrudin‐S mRNA was detected in all tissues examined. With the use of a splicing reporter minigene that produces two distinct fluorescent proteins in a manner dependent on the splicing pattern of protrudin transcripts, we found that most neurons express protrudin‐L, whereas astrocytes express both protrudin isoforms and oligodendrocytes express only protrudin‐S. Protrudin‐L associated to a greater extent with vesicle‐associated membrane protein–associated protein (VAP) than protrudin‐S. Expression of protrudin‐L in hippocampal neurons of protrudin‐deficient mice also promoted neurite outgrowth more efficiently than protrudin‐S. Our results suggest that protrudin‐L is a neuron‐specific protrudin isoform that promotes axonal elongation and contributes to the establishment of neuronal polarity.
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A neural-specific microexon in Protrudin/Zfyve27 increases interaction with VAP and promotes neurite outgrowth.
“A neural-specific microexon in Protrudin/Zfyve27 was recently shown to increase its interaction with the vesicle-associated membrane protein-associated protein (VAP), and to promote neurite outgrowth (Ohnishi et al., 2014)”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Ohnishi et al., 2014
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- © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd conserved switching mechanism of tissue-specific alternative exon selection. PLoS ONE 5, e10946.
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A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains
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“A neural-specific microexon in Protrudin/Zfyve27 was recently shown to increase its interaction with the vesicle-associated membrane protein-associated protein (VAP) and to promote neurite outgrowth (Ohnishi et al., 2014).”
BackgroundRaj, B., & Blencowe, B. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.004 · Cited by 475 · see citing works
Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development
Quesnel-Vallières, M., Irimia, M., Cordes, S. P., & Blencowe, B. J. (2015) · Genes & Development · doi:10.1101/gad.256115.114 · Cited by 155 · see citing works
- Authors
- Ohnishi, T., Shirane, M., Hashimoto, Y., Saita, S., & Nakayama, K. I.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Shirane, Michiko
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2013-11-20
- Volume
- 19
- Issue
- 2
- Pages
- 97-111
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W2007439070
- Cited by
- 33
- References
- 41
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 1 · 2017: 4 · 2015: 4 · 2014: 3
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-09-14)
- Open access
- bronze
- doi.org
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25670517, 25640013)
- RIKEN
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- alternative splicing, microexons, FFAT motif, coiled-coil domain, neuronal polarity, axon elongation, neurite outgrowth, ventilator-associated pneumonia, hippocampal neurons, astrocytes, oligodendrocytes
- MeSH terms
- Animals, Mice, Inbred C57BL, Molecular Sequence Data, Neurons, Organ Specificity, Alternative Splicing, Protein Isoforms, Vesicular Transport Proteins, Cell Line, Tumor, R-SNARE Proteins, Mice
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