TY  - JOUR
AU  - Wang, Jiali
AU  - Platz-Baudin, Eric
AU  - Noetzel-Reiss, Erik
AU  - Offenhäusser, Andreas
AU  - Maybeck, Vanessa
TI  - Expressing Optogenetic Actuators Fused to N-terminal Mucin Motifs Delivers Targets to Specific Subcellular Compartments in Polarized Cells
JO  - Advanced biology
VL  - 8
IS  - 3
SN  - 2366-7478
CY  - Weinheim
PB  - Wiley-VCH
M1  - FZJ-2023-04989
SP  - 2300428
PY  - 2024
AB  - Optogenetics is a powerful approach in neuroscience research. However, other tissues of the body may benefit from controlled ion currents and neuroscience may benefit from more precise optogenetic expression. The present work constructs three subcellularly-targeted optogenetic actuators based on the channelrhodopsin ChR2-XXL, utilizing 5, 10, or 15 tandem repeats (TR) from mucin as N-terminal targeting motifs and evaluates expression in several polarized and non-polarized cell types. The modified channelrhodopsin maintains its electrophysiological properties, which can be used to produce continuous membrane depolarization, despite the expected size of the repeats. This work then shows that these actuators are subcellularly localized in polarized cells. In polarized epithelial cells, all three actuators localize to just the lateral membrane. The TR-tagged constructs also express subcellularly in cortical neurons, where TR5-ChR2XXL and TR10-ChR2XXL mainly target the somatodendrites. Moreover, the transfection efficiencies are shown to be dependent on cell type and tandem repeat length. Overall, this work verifies that the targeting motifs from epithelial cells can be used to localize optogenetic actuators in both epithelia and neurons, opening epithelia processes to optogenetic manipulation and providing new possibilities to target optogenetic tools.
LB  - PUB:(DE-HGF)16
C6  - 38015104
UR  - <Go to ISI:>//WOS:001119680100001
DO  - DOI:10.1002/adbi.202300428
UR  - https://juser.fz-juelich.de/record/1018695
ER  -