LRRC8D (Leucine Rich Repeat Containing 8 VRAC Subunit D)

Furthermore, we mimicked the absence of the neutralizing acetyl moiety that is observed after loss of NAA60 by introducing positively charged amino acids at the N-termini of LRRC8A/D, which indeed decreased cis- and carboplatin sensitivity. Our findings highlight the importance of N-terminal acetylation by NAA60 for effective platinum drug uptake, offering new insights into overcoming drug resistance.

Here we report the intracochlear distribution of all five LRRC8 subunits of VRAC, a volume-regulated anion channel that transports chloride, metabolites and drugs such as the ototoxic anti-cancer drug cisplatin, and explore its physiological role by ablating its subunits...The strong downregulation of Kir4.1 might be secondary to a loss of VRAC-mediated transport of metabolites regulating inner ear redox potential such as glutathione. Our study extends the knowledge of the role of cochlear ion transport in hearing and ototoxicity.

We develop a bispecific T cell engager targeting ILT3 that shows potent killing effects in vitro and decreased tumor burden and prolonged mice survival in vivo, suggesting therapeutic relevance. Our study uncovers MM-associated antigens that hold great promise for immune-based therapies of MM.