PDZD8-mediated lipid transfer at contacts between the ER and late endosomes/lysosomes is required for neurite outgrowth

ABSTRACT Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and late endosomes/lysosomes (LE/lys) are emerging as critical hubs for diverse cellular events, changes in their extents linked to severe neurological diseases. While recent studies show that synaptotagmin-like mitochondrial-lipid-binding (SMP) domain-containing protein PDZD8 may mediate formation of ER–LE/lys MCSs, functions remain largely elusive. Here, we attempt investigate lipid transfer activities extent which its depend on activities. In accordance with studies, demonstrate is a protrudin (ZFYVE27)-interacting acts tether at MCSs. Furthermore, discover SMP domain binds glycerophospholipids ceramides both vivo vitro, can transport lipids membranes vitro. Functionally, required LE/lys positioning neurite outgrowth, dependent activity domain. This article has an associated First Person interview first author paper.