title: Identification and characterization of a neuron-specific isoform of protrudin.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Michiko
authors.initials: M
authors.lastname: Shirane
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Shotaro
authors.initials: S
authors.lastname: Saita
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D050683:R-SNARE Proteins; D033921:Vesicular Transport Proteins; C514783:protrudin protein, mouse