4 research outputs found
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