Abstract
ABSTRACTMembrane trafficking controls vesicular transport of cargo between cellular compartments. Vesicular trafficking is essential for cellular homeostasis and dysfunctional trafficking is linked to several pathologies such as neurodegenerative diseases. Following endocytosis, early endosomes act as sorting stations of internalized materials, routing cargo toward various fates. One important class of membrane trafficking regulators are RAB GTPases. RAB21 has been associated with multiple functions and regulates integrin internalization, endosomal sorting of specific clathrin-independent cargo and autophagy. Although RAB21 is mostly associated with early endosomes, it has been shown to mediate a specific sorting event at the Golgi. From mass spectrometry data, we identified a GTP-favored interaction between RAB21 and TMED10 and 9, essential regulators of COPI and COPII vesicles. Using RAB21 knockout cells, we describe the role of RAB21 in modulating TMED10 Golgi localization. Taken together, our study suggests a new potential function of RAB21 in modulating TMED10 trafficking, with relevance to neurodegenerative disorders.
Highlights
Membrane trafficking, which represents all vesicular exchanges between organelles and cellular compartments, is highly regulated and essential for cellular homeostasis (Vicinanza et al, 2008)
TMED10 interacts indirectly with RAB21 the functional association of TMED10 with ARF1 has been well characterized (D’Souza-Schorey and Chavrier, 2006), potential interactions with RAB family GTPases have only been shown by proteomic analysis (Hein et al, 2015) or genetic screens (Blomen et al, 2015), but have not been further assessed
Our recent mass spectrometry data identified a potential interaction between RAB21, TMED10 and TMED9
Summary
Membrane trafficking, which represents all vesicular exchanges between organelles and cellular compartments, is highly regulated and essential for cellular homeostasis (Vicinanza et al, 2008). With almost 70 members, RABs represent the largest family of small GTPases in humans (Rojas et al, 2012). These proteins mediate each step of vesicular trafficking, from membrane budding to vesicle transport, to fusion with target organelles (Hutagalung and Novick, 2011). Given their roles in trafficking, RABs are tightly regulated (Barr and Lambright, 2010). RABs cycle between their active GTP-bound form and inactive GDP-bound form. RABs recruit a large number of effectors to achieve their functions (Grosshans et al, 2006). RABs can directly interact with cargo to regulate their trafficking (Pellinen et al, 2006)
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