Claudia Weidling's research while affiliated with IT University of Copenhagen and other places

Publications (7)

Article
Full-text available
Depolarizing sodium (Na⁺) leak currents carried by the NALCN channel regulate the resting membrane potential of many neurons to modulate respiration, circadian rhythm, locomotion and pain sensitivity1–8. NALCN requires FAM155A, UNC79 and UNC80 to function, but the role of these auxiliary subunits is not understood3,7,9–12. NALCN, UNC79 and UNC80 ar...
Article
Full-text available
Persistently depolarizing sodium (Na+) leak currents that enhance electrical excitability have been described for decades1,2. The entity responsible for the major background Na+ conductance in neurons had remained a mystery until characterization of NALCN (Na+leak channel, non-selective)3,4. NALCN-mediated currents regulate neuronal excitability li...
Article
Full-text available
The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80,...
Preprint
The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that the robust function of NALCN in heterologous systems requires co-expression of UNC79, UN...

Citations

... An extra interface between the I-II linker of NALCN and UNC79 C-half identified in that work was not observed in our study, probably due to different sample conditions ( Supplementary Fig. S7). It seems that I-II linker is not as essential as the II-III linker in association between NALCN and the UNC79-UNC80 subcomplex, as alterations of the I-II linker did not obviously impact the channelosome function 26 . The absence of the I-II linker interacting interface in our study suggests that it is highly dynamic, which in turn leads to a more pronounced local conformational flexibility (Supplementary Video S1). ...
... However, the auxiliary subunits of the NALCN channelosome are unique and share no sequence homology to the auxiliary subunits of other 4 × 6 TM channels. Among the auxiliary subunits, FAM155A may facilitate the folding and membrane translocation of NALCN through forming a stable subcomplex with NALCN [17][18][19] . UNC79 and UNC80 are large proteins that have been reported indispensable for neuronal localization in mice 9 and robust circadian locomotor rhythms in Drosophila 6 . ...
... NALCN forms a unique complex termed NALCN channelosome with the auxiliary subunits FAM155A, UNC79, and UNC80 [5][6][7] . The formation of the NALCN channelosome is critical to a fully functional Na + conductance carried by NALCN 8 . Knockout of NALCN, UNC79, or UNC80 is lethal in mice 1,9,10 . ...