| RRC ID |
59434
|
| Author |
Alqadah A, Hsieh YW, Xiong R, Lesch BJ, Chang C, Chuang CF.
|
| Title |
A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor.
|
| Journal |
Proc Natl Acad Sci U S A
|
| Abstract |
Stochastic neuronal cell fate choice involving notch-independent mechanisms is a poorly understood biological process. The Caenorhabditis elegans AWC olfactory neuron pair asymmetrically differentiates into the default AWCOFF and induced AWCON subtypes in a stochastic manner. Stochastic choice of the AWCON subtype is established using gap junctions and SLO BK potassium channels to repress a calcium-activated protein kinase pathway. However, it is unknown how the potassium channel-repressed calcium signaling is translated into the induction of the AWCON subtype. Here, we identify a detailed working mechanism of how the homeodomain-like transcription factor NSY-7, previously described as a repressor in the maintenance of AWC asymmetry, couples SLO BK potassium channels to transactivation of sox-2 expression for the induction of the AWCON subtype through the identification of a unique imb-2 (transportin 1) allele. imb-2 loss-of-function mutants are not viable; however, we identify a viable imb-2 allele from an unbiased forward genetic screen that reveals a specific role of imb-2 in AWC olfactory neuron asymmetry. IMB-2 specifically drives nuclear import of NSY-7 within AWC neurons to transactivate the expression of the high mobility group (HMG)-box transcription factor SOX-2 for the specification of the AWCON subtype. This study provides mechanistic insight into how NSY-7 couples SLO BK potassium channels to transactivation of sox-2 expression for the induction of the AWCON subtype. Our findings also provide structure-function insight into a conserved amino acid residue of transportins in brain development and suggest its dysfunction may lead to human neurological disorders.
|
| Volume |
116(50)
|
| Pages |
25137-25146
|
| Published |
2019-12-10
|
| DOI |
10.1073/pnas.1908168116
|
| PII |
1908168116
|
| PMID |
31767767
|
| PMC |
PMC6911211
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / physiology
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Calcium Signaling / physiology
Cell Nucleus / metabolism*
Gap Junctions / metabolism
Karyopherins / genetics
Karyopherins / metabolism*
Olfactory Receptor Neurons / metabolism*
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism*
Stochastic Processes
|
| IF |
9.58
|
| Times Cited |
0
|
| Resource |
| C.elegans |
tm1303
tm6328
tm6405
tm3036
tm1100
tm7139 |
