An endocytic signal for the potassium channel KCNK3

Membrane trafficking is a major cellular mechanism for the regulation of surface expression of plasma membrane proteins. Recently, a carboxyl terminus motif, FREKLAYAIA, has been shown to control the internalization of the dopamine transporter (DAT), a critical protein in synaptic transmission. Sequence comparison across BLAST identified a similar carboxyl motif, SREKLQYSIP, in the leak potassium channel KCNK3. The current study tested whether this motif was necessary and sufficient for the internalization of the channel. Our results suggest that the carboxyl terminus of KCNK3 is sufficient for the internalization of an endocytic deficient reporter molecule (Tac), and that the SREKLQYSIP motif may be necessary for this internalization

Albumin-Oxanorbornadiene Conjugates Formed <i>ex Vivo</i> for the Extended Circulation of Hydrophilic Cargo

Oxanorbornadiene dicarboxylate (OND) reagents were explored for the purpose of binding and releasing chemical cargos from endogenous circulating serum albumins. ONDs bearing gadolinium chelates as model cargos exhibited variable conjugation efficiencies with albumin in rat subjects that are consistent with the observed reactivity of each linker and their observed stability toward serum hydrolases <i>in vitro</i>. The terminal elimination rate from circulation was dependent on the identity of the OND used, and increased circulation time of gadolinium cargo was achieved for linkers bearing electrophilic fragments designed to react with cysteine-34 of circulating serum albumin. This binding of and release from endogenous albumin highlights the potential of OND linkers in the context of optimizing the pharmacokinetic parameters of drugs or diagnostic agents