| First Author | Alqadah A | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 50 | Pages | 25137-25146 |
| PubMed ID | 31767767 | Mgi Jnum | J:287844 |
| Mgi Id | MGI:6382379 | Doi | 10.1073/pnas.1908168116 |
| Citation | Alqadah A, et al. (2019) A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor. Proc Natl Acad Sci U S A 116(50):25137-25146 |
| abstractText | 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 AWC(OFF) and induced AWC(ON) subtypes in a stochastic manner. Stochastic choice of the AWC(ON) 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 AWC(ON) 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 AWC(ON) 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 AWC(ON) 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 AWC(ON) 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. |
