DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes

In this study, we characterized cellular roles of FAM45A. We found that FAM45A localized mainly in late/multivesicular endosomes. Depletion of FAM45A resulted in clustering of endosomes to the perinuclear region. The endocytosis of EGF receptor was impaired in FAM45A knockdown cells due to a delay in the early-to-late endosome transition. Furthermore, the secretion of selected exosome subpopulations was also attenuated in FAM45A knockdown cells. Consistent with these results, Rab27a and Rab27b, two Rabs involved in endosome motility and exosome biogenesis, were found to act downstream of FAM45A pathway. FAM45A colocalized with Rab27a/b and formed complex with them in a nucleotide-dependent manner. Taken together, FAM45A defines a novel regulatory step in the homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as Rab27a/b.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research