Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms

Karen Yap, Yixin Xiao, Brad A. Friedman, H. Shawn Je, Evgeniy V. Makeyev

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)
260 Downloads (Pure)

Abstract

Alternative splicing (AS) is an important source of proteome diversity in eukaryotes. However, how this affects protein repertoires at a single-cell level remains an open question. Here, we show that many 3′-terminal exons are persistently co-expressed with their alternatives in mammalian neurons. In an important example of this scenario, cell polarity gene Cdc42, a combination of polypyrimidine tract-binding, protein-dependent, and constitutive splicing mechanisms ensures a halfway switch from the general (E7) to the neuron-specific (E6) alternative 3′-terminal exon during neuronal differentiation. Perturbing the nearly equimolar E6/E7 ratio in neurons results in defects in both axonal and dendritic compartments and suggests that Cdc42E7 is involved in axonogenesis, whereas Cdc42E6 is required for normal development of dendritic spines. Thus, co-expression of a precise blend of functionally distinct splice isoforms rather than a complete switch from one isoform to another underlies proper structural and functional polarization of neurons.
Original languageEnglish
Pages (from-to)1316-1328
JournalCell Reports
Volume15
Issue number6
Early online date28 Apr 2016
DOIs
Publication statusPublished - 10 May 2016

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