Molecular machinery regulating organelle dynamics during axon growth and guidance

Axon growth and guidance in the developing nervous system rely on intracellular membrane dynamics that involve endosome maturation and transport, as well as its regulated tethering to the endoplasmic reticulum (ER). Recent studies have identified several key molecules, such as protrudin, which plays a dynamic role at membrane contact sites between the ER and endosomes/lysosomes, and myosin Va, which acts as a sensor for ER-derived Ca²⁺ that triggers peri-ER membrane export. These molecules form different types of multiprotein complexes at the interface of organelles and, in response to their surrounding microenvironments, such as Ca²⁺ concentrations and lipid contents, regulate the directional movement of endosomal vesicles in extending axons. Here, we review the molecular mechanisms underlying membrane dynamics and inter-organelle interactions during neuronal morphogenesis.