First Author | Shakya S | Year | 2018 |
Journal | EMBO Rep | Volume | 19 |
Issue | 12 | PubMed ID | 30404817 |
Mgi Jnum | J:269335 | Mgi Id | MGI:6259953 |
Doi | 10.15252/embr.201845918 | Citation | Shakya S, et al. (2018) Rab22A recruits BLOC-1 and BLOC-2 to promote the biogenesis of recycling endosomes. EMBO Rep 19(12) |
abstractText | Recycling endosomes (REs) are transient endosomal tubular intermediates of early/sorting endosomes (E/SEs) that function in cargo recycling to the cell surface and deliver the cell type-specific cargo to lysosome-related organelles such as melanosomes in melanocytes. However, the mechanism of RE biogenesis is largely unknown. In this study, by using an endosomal Rab-specific RNAi screen, we identified Rab22A as a critical player during RE biogenesis. Rab22A-knockdown results in reduced RE dynamics and concurrent cargo accumulation in the E/SEs or lysosomes. Rab22A forms a complex with BLOC-1, BLOC-2 and the kinesin-3 family motor KIF13A on endosomes. Consistently, the RE-dependent transport defects observed in Rab22A-depleted cells phenocopy those in BLOC-1-/BLOC-2-deficient cells. Further, Rab22A depletion reduced the membrane association of BLOC-1/BLOC-2. Taken together, these findings suggest that Rab22A promotes the assembly of a BLOC-1-BLOC-2-KIF13A complex on E/SEs to generate REs that maintain cellular and organelle homeostasis. |