DNAJC13 localization to endosomes is opposed by its J domain and its disordered C-terminus.

ABSTRACT: Endosomes are a central sorting hub for membrane cargos. DNAJC13/RME-8 plays a critical role in endosomal trafficking by regulating the endosomal recycling and degradative pathways. DNAJC13 localizes to endosomes through its N-terminal Pleckstrin Homology (PH)-like domain, which binds endosomal phosphatidylinositol-3-phosphate (PI(3)P). However, little is known about how DNAJC13 localization is regulated. Here, we show that two regions within DNAJC13, its J domain and disordered C-terminus, act as negative regulators of its PH-like domain. Using a structure-function approach, we map these control points to a conserved YLT motif in the disordered C-terminus as well as the catalytic HPD triad in its J domain. Mutation of either motif enhances DNAJC13 endosomal localization in cells and incre

SUBMITTER: Adoff H 

PROVIDER: S-EPMC12404652 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature