Abstract
AbstractWe identified kazrin C as a human protein that inhibits clathrin-mediated endocytosis when overexpressed. We now generated kazrin knock out and GFP-kazrin C expressing MEF lines to investigate in detail its function in endocytic traffic. We find that kazrin depletion delays recycling of internalized material and causes accumulation and dispersal of early endosomes (EE), indicating a role in transport from the early to the perinuclear recycling endosomes (RE). Consistently, we found that the C-terminal domain of kazrin C, predicted to be an intrinsically disordered region (IDR), specifically interacts with several endosomal components, including Epsin Homology Domain (EHD) proteins, γ-adaptin, and phosphatidyl-inositol-3 phosphate. Further, kazrin C shares homology with dynein/dynactin adaptors, it directly interacts with the dynactin complex and the dynein light intermediate chain LIC1, and overexpressed GFP-kazrin C forms condensates that entrap EE in the vicinity of the centrosome, in a microtubule-dependent manner. Altogether, the data indicates that kazrin C facilitates cargo recycling by trapping EE or EE-derived transport intermediates at the perinuclear region, where transfer of cargo to the RE might occur.
Publisher
Cold Spring Harbor Laboratory