Orthodenticle homeobox 2 is transported to lysosomes by nuclear budding vesicles.

ABSTRACT: Transcription factors (TFs) are transported from the cytoplasm to the nucleus and disappear from the nucleus after they regulate gene expression. Here, we discover an unconventional nuclear export of the TF, orthodenticle homeobox 2 (OTX2), in nuclear budding vesicles, which transport OTX2 to the lysosome. We further find that torsin1a (Tor1a) is responsible for scission of the inner nuclear vesicle, which captures OTX2 using the LINC complex. Consistent with this, in cells expressing an ATPase-inactive Tor1aΔE mutant and the LINC (linker of nucleoskeleton and cytoskeleton) breaker KASH2, OTX2 accumulated and formed aggregates in the nucleus. Consequently, in the mice expressing Tor1aΔE and KASH2, OTX2 could not be secreted from the choroid plexus for transfer to the visual cortex, leading

SUBMITTER: Park JW 

PROVIDER: S-EPMC9971051 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature