Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation

• DOI: 10.1038/s41467-020-18413-9
• Publication Date: 2020-09-11T10:09:21Z
• Authors: Michiko Shirane; Mariko Wada; Keiko Morita; Nahoki Hayashi; Reina Kunimatsu; Yuki Matsumoto; Fumiko Matsuzaki; Hirokazu Nakatsumi; Keisuke Ohta; Yasushi Tamura; Keiichi I. Nakayama
• Keywords: Vesicular Transport Proteins

Endosome maturation depends on membrane contact sites (MCSs) formed between endoplasmic reticulum (ER) and endolysosomes (LyLEs). The mechanism underlying lipid supply for this process its pathophysiological relevance remains unclear, however. Here, we identify PDZD8-the mammalian ortholog of a yeast ERMES subunit-as protein that interacts with protrudin, which is located at ER-LyLE MCSs. Protrudin PDZD8 promote the formation MCSs, shows ability to extract various lipids from ER. Overexpression both protrudin in HeLa cells, as well their depletion mouse primary neurons, impairs endosomal homeostasis by inducing abnormal large vacuoles reminiscent those apparent spastin- or REEP1-deficient neurons. protrudin-PDZD8 system also essential establishment neuronal polarity. Our results suggest cooperatively endosome mediating tethering extraction thereby maintaining polarity integrity.