Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms
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 30-terminal exons are persistently co-expressed with their alternatives in mammalian neuro...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2017
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/83051 http://hdl.handle.net/10220/42371 |
| _version_ | 1811694638419935232 |
|---|---|
| author | Yap, Karen Xiao, Yixin Friedman, Brad A. Je, H. Shawn Makeyev, Eugene V. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Yap, Karen Xiao, Yixin Friedman, Brad A. Je, H. Shawn Makeyev, Eugene V. |
| author_sort | Yap, Karen |
| collection | NTU |
| description | 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 30-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
30-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. |
| first_indexed | 2024-10-01T07:10:45Z |
| format | Journal Article |
| id | ntu-10356/83051 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:10:45Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/830512023-02-28T17:00:11Z Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms Yap, Karen Xiao, Yixin Friedman, Brad A. Je, H. Shawn Makeyev, Eugene V. School of Biological Sciences Eukaryotic proteomes Cdc42 in neurons 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 30-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 30-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. NMRC (Natl Medical Research Council, S’pore) Published version 2017-05-11T06:00:04Z 2019-12-06T15:10:53Z 2017-05-11T06:00:04Z 2019-12-06T15:10:53Z 2016 Journal Article Yap, K., Xiao, Y., Friedman, B. A., Je, H. S., & Makeyev, E. V. (2016). Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms. Cell Reports, 15(6), 1316-1328. 2211-1247 https://hdl.handle.net/10356/83051 http://hdl.handle.net/10220/42371 10.1016/j.celrep.2016.04.012 27134173 en Cell Reports © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 14 p. application/pdf |
| spellingShingle | Eukaryotic proteomes Cdc42 in neurons Yap, Karen Xiao, Yixin Friedman, Brad A. Je, H. Shawn Makeyev, Eugene V. Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms |
| title | Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms |
| title_full | Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms |
| title_fullStr | Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms |
| title_full_unstemmed | Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms |
| title_short | Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms |
| title_sort | polarizing the neuron through sustained co expression of alternatively spliced isoforms |
| topic | Eukaryotic proteomes Cdc42 in neurons |
| url | https://hdl.handle.net/10356/83051 http://hdl.handle.net/10220/42371 |
| work_keys_str_mv | AT yapkaren polarizingtheneuronthroughsustainedcoexpressionofalternativelysplicedisoforms AT xiaoyixin polarizingtheneuronthroughsustainedcoexpressionofalternativelysplicedisoforms AT friedmanbrada polarizingtheneuronthroughsustainedcoexpressionofalternativelysplicedisoforms AT jehshawn polarizingtheneuronthroughsustainedcoexpressionofalternativelysplicedisoforms AT makeyeveugenev polarizingtheneuronthroughsustainedcoexpressionofalternativelysplicedisoforms |